Information

Are free-nuclear division and endomitosis the same?

Are free-nuclear division and endomitosis the same?


We are searching data for your request:

Forums and discussions:
Manuals and reference books:
Data from registers:
Wait the end of the search in all databases.
Upon completion, a link will appear to access the found materials.

As far as I understood it, both are cases of karyokinesis, not followed by cytokinesis.


No. If you google the terms you'll get a lot of sites with definitions. For example:

Nuclear division

Definition

noun

The process by which a nucleus divides, resulting in the segregation of the genome to opposite poles of a dividing cell.

source: http://www.biology-online.org/dictionary/Nuclear_division

Edit:

or

free nuclear division mitotic division of nuclei without accompanying cytokinesis, i.e. nuclei divide in a common cytoplasm, the cells walls only forming around each later

source: http://ecflora.cavehill.uwi.edu/bio_courses/bl14apl/Gloss.htm

versus

endomitosis mitosis taking place without dissolution of the nuclear membrane, and not followed by cytoplasmic division, resulting in doubling of the number of chromosomes within the nucleus.

source: http://medical-dictionary.thefreedictionary.com/endomitosis

or a bit more revealing:

Duplicated chromosomes produced by endomitosis exist as discrete units in a single polyploid nucleus or may be packaged into separate nuclei, depending on the phase at which mitosis is aborted

source: http://en.wikipedia.org/wiki/Endoreduplication

So as you see by definition nuclear division is part of a bigger process (cell division), and accoriding to the first source karyokinesis is a synonim for nuclear division (karyo = nucleus kinesis = moving, both come form greek language).

Edit:

If you check the definition above, you can see that free-nuclear division is a mitosis without cytokinesis, thus chromosome separation still occurs.

In endomitosis the can end up with a polyploid nucleus, in contrast to the other two aforementioned mechanism where no polyploidy occurs.


In the cases of pollen grains free nuclear division occurs. entering into the s phase the chromosome no remains as 46 but the DNA doubles ie 4n condition occurs. During the anaphase the sister chromatids separate and reaches both ends. And when telo phase occurs nuclear membrane is surrounded around 2 genetic material. But cytokinesis is blocked there. But when again this cell enters s phase there again the genetic material replicated ie 2 nucleus having 4n condition is formed.this is free nuclear mitosis. These chromosomes doesn't separate in anaphase due to failure in attachment of spindle fibres. So karyokinesis also get stopped resulting cell to 8n condition or polyploidy. This is endomitosis


Phases of Mitosis | Cell Division

During prophase, the individual chromosome appears in double threaded struc­ture composed of two chromatids from the beginning. During this phase, the volume of the chromosomes too increases considerably and there is initiation of coiling leading to shortening and thickening of chromatids. As prophase advances there is a tendency of chromosomes to move towards the periphery of the nucleus.

Mitosis: Phase # 2. Metaphase:

The onset of metaphase marks the dissolution of nuclear membrane and nucleo­lus, formation of spindle, and chromosomes arrange themselves in the centre of cell-equator, the centromere being attached, to the spindle fibres which constitute the spindle.

The arrange­ment of the centromeres is in the form of a ring which together constitute the metaphase plate. Based on the position of the centromeres, chro­mosomes appear as V or J or simple rod-like depending on the morphology of chromosome metacentric, acrocentric or telocentric. The chro­mosomes at metaphase are highly spiralized.

Mitosis: Phase # 3. Anaphase:

The onset of anaphase marks the division of chromosome into two longitudinal halves, and triggers their movements towards the two opposite poles. The movement of the homo­logous centromeres to the opposite poles is faci­litated by shortening of the fibres thus dragging the chromosomes towards the poles. The com­pletion of the movement of chromosomes to the two opposite poles marks the end of anaphase.

Mitosis: Phase # 4. Telophase:

During telophase, the two sets of chromatids at the two poles become organized into two sets of chromosomes, start uncoiling from the coiled state and lose their chromaticity. De-spiralization and de-condensation along with hydration are associated with the formation of nuclear membrane and nucleolus resulting in two daughter nuclei.

The telophase stage is followed later by the formation of cell plate, dividing the cell into two daughter cells, each carrying the same chromosome numbers as the original.

The process of chromosome duplication without cell division is called endomitosis. In this process a cell with successive S phases without entering into divisional phase subjected to endopolyploidy. This resulted in polytene chromosomes as found typically in the salivary gland of Drosophila as well as in tapetum, endosperm and suspensor of many plants.

They arise due to repeated longitudinal splitting’s of chromatids and consequent non-separation of split portions.


GENETICS OF MICROORGANISMS | Fungi

Rajat Sandhir , . D.R. Modi , in Encyclopedia of Food Microbiology , 1999

Mitosis

Nuclear division , mitosis, which takes place during the process of vegetative reproduction, ensures the division of genetic material between the two newly formed cells. The classical mitosis has a number of stages.

After the nuclear resting period, the interphase, a preparatory phase, the prophase begins. During this phase, the nuclear matter is arranged into chromosomes that can be readily stained. The chromosomes are at first long and thin, often coiled so that they can not be counted. Later, they become thicker and shorter and assume a clearly double ribbon-like structure. The doubling of chromosomes gives rise to two ribbon-like structures, the chromatids, which are situated close to each other and are firmly bound by the centromere. The centrioles in the cytoplasm separate and move to opposite poles and the formation of a spindle begins. The nucleolus and nuclear membrane disappear during this stage.

During metaphase the double chromosomes aggregate in the equatorial plane of the spindle. In metaphase of the cell division, chromosomes can be seen with light microscope as compact structures. The DNA is quiescent at this stage serving as a template. The metaphase chromosome is analogous to the quiescent DNA molecule of the infective resting phage particle, packaged for transit to a future host cell. Figure 4 shows the typical structure of metaphase chromosome. The chromosomes are attached to the spindle by their centromeres.

Figure 4 . Typical structure of metaphase chromosome. Each chromatid contains two identical DNA molecules created earlier in the cell cycle by the process of DNA replication and the two chromatids are held by a centromere.

The anaphase is the third stage of nuclear division during which the pair of chromosomes separate and migrate to opposite poles of the nucleus.

During telophase, the last stage of mitotic division, the nuclei and nuclear membrane reappear, and the two new nuclei are formed.

In fungi, nonclassical mitosis takes place without the disruption of the nuclear membrane, i.e. endomitosis the division is also referred to as intranuclear ( Fig. 5 ). The nuclear membrane constricts in a dumbbell like fashion and eventually separates into two daughter nuclei. It is believed that the nuclear division without the disruption of the nuclear membrane is advantageous in fungi, which generally have many nuclei in the cytoplasm, in avoiding mixing of chromosomes during division. Similarly, the nucleolus is usually retained during mitosis and may be stretched out and divided between the daughter nuclei. In some fungi, however, the nucleolus is either lost out of the nucleus, disperses and disappears within the nucleus, or disperses within the nucleus but remains detectable during mitosis. In some fungi, centrioles have not been detected and instead there are spindle pole bodies as electron-dense cytoplasmic structures that lie adjacent to the nuclear envelope in most true fungi. Spindle pole bodies are microtubule organizing centres during mitosis and meiosis and have a similar function to that carried out by centrioles in other eukaryotes. In most fungi, the chromosomes are randomly distributed during metaphase and do not define the equatorial plate that is commonly observed in other eukaryotes.

Figure 5 . Diagrammatic illustration of the process of mitosis in fungi. Note that the nuclear envelope and nucleolus do not disappear and the chromosomes are randomly distributed at the equatorial plate.


Genomics of Endometriosis

Whereas genetics refers to the heritability of a trait, genomics refers to how genes are expressed. At the most fundamental level, the genome is a list of the DNA sequences of all of the chromosomes with annotation of genes, introns and exons, promoters, and regulatory sequences. Genomics can be defined as any study that takes a global approach to examination of a genome we will define it here as studies of global gene expression. The DNA microarray is one of the most important tools of genomics.

DNA microarray technology

All of the cells in our bodies contain the same set of chromosomes with the same set of genes, the genome, but each differentiated cell type expresses only a fraction of the total available genes. DNA microarray technology allows a determination of which genes are expressed in a given cell type under basal conditions. Perhaps more importantly, the technology can measure changes in gene expression in response to disease, inflammation, pharmaceutical agents, hormones, growth factors, developmental changes, or other deviations from homeostasis. In regard to endometriosis, DNA microarrays allow a determination of gene expression under basal conditions and in the presence of the disease. Examples of medical advances that can be made based on insights into gene expression include the development of better treatments of disease and new diagnostic tests, as well as a better understanding of the pathology of disease these concepts are relevant to endometriosis as well as other diseases.

Methods for obtaining RNA for analysis of gene expression in endometriosis have been described for intact eutopic and ectopic endometrial tissue. 25 DNA microarray technology takes advantage of the fundamental nature of DNA and RNA to bind to complementary strands of nucleic acids. 26 On a DNA microarray, single-stranded sequences of DNA, corresponding to specific genes, are arrayed on a matrix such as a glass microscope slide or a cassette. RNA is extracted from the tissue or cells of interest and incubated with the microarray. The complementary base pairing sequence structure of DNA and RNA allows the RNA in the sample to bind to the DNA sequence on the microarray. The gene sequences on the microarray to which RNA from the tissue sample bound are identified to develop gene expression profiles for that tissue.

Gene expression profiles in endometriosis

Two experimental paradigms have been used to examine the genomics of endometriosis: (1) Comparison of gene expression of eutopic endometrium to ectopic endometrium of the same patient 25, 27 or the same animal in animal models 28 , and (2) Comparison of eutopic endometrium from women with endometriosis to eutopic endometrium from women without endometriosis. 29-31 The goals of the two approaches are different. When eutopic and ectopic endometrium are compared from women with endometriosis, the goals include identification of unique features of the ectopic endometrium that could lead to better treatments for endometriosis through identification of new therapeutic targets or to noninvasive diagnostic tests for endometriosis. This type of data will also lead to a better understanding of the pathology of the disease. The goals of comparing eutopic endometrium from women with endometriosis to that from women without endometriosis include a search for factors that may prevent implantation in women with endometriosis (i.e., the causative factors of endometriosis-associated infertility), identification of factors in endometrium that could trigger development of endometriosis when the endometrium escapes from the uterus (in support of the hypothesis that the endometrium of women who develop endometriosis is different from that of women who do not develop the disease), and a predictive measure to determine which women might develop endometriosis.

The two most useful types of information that can be derived from DNA microarray data are lists of differentially expressed genes and groupings of differentially expressed genes into related functional groups (also called gene ontologies). Lists of individual genes that are up- or down-regulated are especially useful as a means of identifying potential targets for diagnostic tests or for new treatments. Specialty software programs such as Ariadne Pathway Studio (v6.2, Ariadne Genomics, Rockville, MD) use lists of differentially expressed genes to search for common regulatory factors in an attempt to identify the upstream ligands responsible for the aberrant gene expression in a disease state such as endometriosis. The identification of families of genes that are up- or down-regulated can shed light on pathological etiologies. Gene ontologies may identify differentially expressed gene families that overlap from different research groups using different microarray platforms when comparisons of individual genes do not show overlap. Both of these means of analyzing data are valuable to our understanding of cellular events in endometriosis.

If we examine data obtained from DNA microarray experiments that compared gene expression in eutopic endometrium to that of ectopic endometrium, only 10 genes showed differential expression in three or more experiments in human studies. The list includes caldesmon 1, CD14 antigen, cholinergic receptor muscarinic 3, complement component 1r, myosin heavy polypeptide 11 (MYH11), phorbol-12-myristate-12-acetate-induced protein 1, retinoic acid receptor responder 1, ribonuclease A family 1, thrombospondin 1 (THBS1), and tissue inhibitor of metalloproteinase 3 (TIMP3) ( Table 1 ). There are a number of valid reasons for the lack of overlap among the different microarray studies. Many of the data sets were published before whole human genome microarrays were available. Those experiments used arrays with only a fraction of the genes in the genome, and platforms from different manufacturers contained different subsets of the genome. Thus the overlap among reported datasets can only be as complete as the overlap of genes on the microarrays that were used. Other reasons for the shortness of the list of overlapping genes include variability among human subjects, samples that may have been obtained in the proliferative versus the secretory phase of the reproductive cycle, and the hypothesis that endometriosis samples may be different in lesions obtained from ovarian versus peritoneal versus deep pelvic lesions. 32 There are also differences in the reliability of different microarray platforms.

Table 1

Differential gene expression between eutopic and ectopic endometrium: confirmed in greater than or equal to 3 human DNA microarray studies.

Accession No. Gene Name Gene Ontology
<"type":"entrez-nucleotide","attrs":<"text":"NM_033139","term_id":"261490656","term_text":"NM_033139">> NM_033139 caldesmon 1 (CALD1)Cytoskeleton
<"type":"entrez-nucleotide","attrs":<"text":"NM_000591","term_id":"1519312626","term_text":"NM_000591">> NM_000591 CD14 antigen (CD14)Defense
<"type":"entrez-nucleotide","attrs":<"text":"NM_000740","term_id":"1113820504","term_text":"NM_000740">> NM_000740 cholinergic receptor, muscarinic 3 (CHRM3)Signal transduction
<"type":"entrez-nucleotide","attrs":<"text":"NM_001733","term_id":"1519244396","term_text":"NM_001733">> NM_001733 complement component 1r (C1R)Defense
<"type":"entrez-nucleotide","attrs":<"text":"NM_002474","term_id":"1519313911","term_text":"NM_002474">> NM_002474 myosin, heavy polypeptide 11 (MYH11)Cytoskeleton
<"type":"entrez-nucleotide","attrs":<"text":"NM_021127","term_id":"1677499502","term_text":"NM_021127">> NM_021127 phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)Signal transduction
<"type":"entrez-nucleotide","attrs":<"text":"NM_206963","term_id":"1519243841","term_text":"NM_206963">> NM_206963 retinoic acid receptor responder 1 (RARRES1)Cell cycle
<"type":"entrez-nucleotide","attrs":<"text":"NM_198235","term_id":"1674996448","term_text":"NM_198235">> NM_198235 ribonuclease, RNase A family, 1 (RNASE1)Nucleic acid regulation
<"type":"entrez-nucleotide","attrs":<"text":"NM_003246","term_id":"1653961217","term_text":"NM_003246">> NM_003246 thrombospondin 1 (THBS1)Extracellular matrix
<"type":"entrez-nucleotide","attrs":<"text":"NM_000362","term_id":"1787388357","term_text":"NM_000362">> NM_000362 tissue inhibitor of metalloproteinase 3 (TIMP3)Proteinase regulation

The ten genes identified in endometriosis microarray studies listed above show few obvious relationships to each other. Two of the genes share the gene ontology of defense, two are cytoskeleton genes, and two others share the ontology of signal transduction. Application of the bioinformatics software Ariadne Pathway Studio (v6.2, Ariadne Genomics) identified additional relationships. For example, expression of four of the genes (THBS1, TIMP3, CD14, and MYH11) is regulated by the transcription factor SP1 and by the transforming growth factor 㬡 signal transduction pathway. Three of those genes (THBS1, TIMP3, and CD14) appear to also share regulation by additional factors (mitogen-activated protein kinases 1 and 14, protein kinase C, interleukin 6, nuclear factor- 㮫, and jun). The sharing of regulatory factors by these genes implicates those factors in endometriosis. It is likely that additional genes that are regulated by these factors are also involved in endometriosis but are not on the list in because of the limitations of the microarray studies described above.

When data from DNA microarray studies of ectopic versus eutopic endometriosis in humans 25, 27 are merged with microarray data from surgically induced animal models of endometriosis 28 the number of differentially expressed genes is more extensive (data not shown). The list of differentially expressed genes is longer because most of the microarrays used for animal studies used whole genome arrays which allow more complete analysis of gene expression. Each gene ontology identified by the human studies is expanded in the merged list of genes. In descending order, the ontologies include signal transduction (50 genes), defense (including inflammatory and immune response genes, 43 genes), proteinases and their regulators (26 genes), cell cycle (25 genes), cytoskeleton (14 genes) and extracellular matrix (13 genes). Two new ontologies, transcriptional regulation (20 genes) and cell adhesion (17 genes) were added to the list of ontologies when data from animal studies were merged with the human data. Recently, Zhao and coworkers 33 took the analysis of gene ontologies a step further by performing a gene set enrichment analysis on endometriosis microarray data that had been deposited in public databases. Their results identified that pathways related to the immune system and immune disorders are highly up-regulated in endometriosis. 33

Data from genomics studies support many of the hypotheses regarding the etiology of endometriosis. For example, changes in cell adhesion factors and proteinases and their regulators that have been proposed to play a role in the adhesion and invasion of endometrial tissue in the development of endometriosis 32 are shown to be up-regulated in genomics studies. 33 Moreover, angiogenic factors, growth factors, and hormone receptor genes are also up-regulated in the genomic studies. 18 Perhaps the most interesting aspect of the gene expression studies is the highlighting of the up-regulation of inflammatory response gene. 25, 33 The inflammatory nature of endometriosis has long been recognized 32 the genomics studies further advance the concept that aberrant communication between ectopic endometrial cells and immune system cells participating in the inflammatory response contribute to the development and persistence of endometriosis. 25, 34 Collectively, the studies cited above support the hypothesis that endometriosis is the result of abnormal expression or regulation of certain key genes.

Eutopic endometrium of women with endometriosis versus endometrium of women without endometriosis

Three publications have addressed the genomics of endometrium of women with endometriosis compared to that of women without endometriosis. 29-31 Of the genes reported by these three groups (266 total genes reported), only one was identified as differentially expressed in more than one of the studies. Solute carrier family 1, member 1 [SLC1A1] was down-regulated in 2 of the 3 studies. The lack of overlap among these three studies is disturbing however, the same caveats described above apply here. None of these groups used whole genome DNA microarrays. Moreover, the experiments were not designed to determine whether the differential expression of genes in eutopic endometrium was a result of the presence of endometriosis or a cause of the disease.

Genomics studies have increased the depth of our understanding of the underlying pathology of endometriosis and have highlighted the role of the immune system in endometriosis. However, genomics studies have not yet delivered on the hope of noninvasive diagnostic tests for endometriosis. Moreover, new treatments based on our increased understanding of the disease remain in the future.


NCERT Solutions For Class 11 Biology Cell Cycle and Cell Division

1. What is the average cell cycle span for a mammalian cell?
Solnution: 24 hours.

2. Distinguish cytokinesis from karyokinesis.
Solnution: Differences between cytokinesis and karyokinesis are:

3. Describe the events taking place during interphase.
Solnution: The interphase, though called the resting phase, is metabolically quite active. It is the time during which the cell prepares itself for division by undergoing both cell growth and DNA replication in an orderly manner. The interphase is further divided into three phases:
• G1 (Gap 1) phase
• S (Synthesis) phase
• G2 (Gap 2) phase
G1 phase corresponds to the interval between mitosis of previous cell cycle and initiation of DNA replication. During G1 phase the cell is metabolically active and grows continuously but does not replicate its DNA S or synthesis phase marks the period during which DNA synthesis or replication takes place. During this time the amount of DNA doubles per cell. In animal cells, during the S phase, DNA replication occurs in the nucleus, and the centriole duplicates in the cytoplasm. During the G2 phase synthesis of DNA stops while cell growth continues with synthesis of protein and RNA in preparation for mitosis.

4. What is G0 (quiescent phase) of cell cycle?
Solnution: G0 phase is the phase of inactivation of cell cycle due to non-availability of mitogens and energy rich compounds. Cells in this stage remain metabolically active but no longer proliferate i.e., do not grow or differentiate unless called on to do so depending on the requirement of the organism. E.g., Nerve and heart cells of chordates are in permanent G0 phase.

5. Why is mitosis called equational division?
Solnution: Mitosis is a type of cell division in which chromosomes replicate and become equally distributed in two daughter nuclei so that the daughter cells come to have the same number and type of chromosomes as present in parent cell. So mitosis is called as equational division.

6. Name the stage of cell cycle at which each one of the following events occur:
(i) Chromosomes are moved to spindle equator.
(ii) Centromere splits and chromatids
separate.
(iii) Pairing between homologous chromo-somes takes place.
(iv) Crossing over between homologous chromosomes takes place.
Solnution:
(i) Metaphase
(ii) Anaphase
(iii) Zygotene of prophase I of meiosis 1
(iv) Pachytene of prophase I of meiosis I

7. Describe the following:
(a) Synapsis
(b) Bivalent
(c) Chiasmata
Draw a diagram to illustrate your answer.
Solnution:
(a) Synapsis: During zygotene of prophase I stage homologou s chromosomes start pairing together and this process of association is called synapsis. Electron micrographs of this stage indicate that chromosome synapsis is accompanied by the formation of complex structure called synaptonemal complex.
(b) Bivalent: The complex formed by a pair of synapsed homologous chromosomes is called a bivalent or a tetrad i.e., 4 chromatids or a pair of chromosomes.

(c) Chiasmata: The beginning of diplotene is recognized by the dissolution of the synaptonemal complex and the tendency of the synapsed homologous chromosomes of the bivalents to separate from each other except at the sites of crossovers. These points of attachment (X-shaped structures) between the homologous chromosomes are called chiasmata.

8. How does cytokinesis in plant cells differ from that in animal cells?
Solnution: Plant cytokinesis and animal cytokinesis differ in following respects:

9. Find examples where the four daughter cells from meiosis are equal in size and where they are found unequal in size.
Solnution: During formation of male gametes (i.e., spermatozoa) in a typical mammal (i.e., human being), the four daughter cells formed from meiosis are equal in size. On the other hand, during formation of female gamete (i.e., ovum) in a typical mammal (i.e., human being), the four daughter cells are unequal in size.

10. Can there be DNA replication without cell division?
Solnution: Yes. Endomitosis is the multiplication of chromosomes present in a set in nucleus without karyokinesis and cytokinesis result-ing in numerous copies within each cell. It is of 2 types.
Polyteny: Here chromosomes divide and redivide without separation of chromatids so that such chromosomes become multistranded with many copies of DNA. Such polytene (many stranded) chromosomes remain in permanent prophase stage and do not undergo cell cycle e.g., polytene (salivary glands) chromosome of Drosophila has 512- 1024 chromatids. Here number of sets of chromosomes does not change.
Polyploidy (endoduplication) : Here all chromosomes in a set divide and its chromatids separate but nucleus does not divide. This results in an increase in number of sets of chromosomes in the nucleus (4x, 8x….). This increase in sets of chromosomes is called polyploidy. It can be induced by colchicine and granosan. These chromosomes are normal and undergo cell cycle.

11. List the main differences between mitosis and meiosis.
Solnution:

12. Distinguish anaphase of mitosis from anaphase I of meiosis.
Solnution: Anaphase of mitosis : It is the phase of shortest duration. APC (anaphase promoting complex) develops. It degenerates proteins -binding the two chromatids in the region of centromere. As a result, the centromere of each chromosome divides. This converts the two chromatids into daughter chromosomes each being attached to the spindle pole of its side by independent chromosomal fibre. The chromosomes move towards the spindle poles with the centromeres projecting towards the poles and the limbs trailing behind. There is corresponding shortening of chromosome fibres. The two pole-ward moving chromosomes of each type remain attached to each other by interzonal fibres. Ultimately, two groups of chromosomes come to lie at the spindle poles.

Anaphase I of meiosis : Chiasmata disappear completely and the homologous chromosomes separate. The process is called disjunction. The separated chromosomes (univalents) show divergent chromatids and are called dyads. They move towards the spindle poles and ultimately form two groups of haploid chromosomes.

13. What is the significance of meiosis?
Solnution: The significance of meiosis is given below:
(i) Formation of gametes – Meiosis forms gametes that are essential for sexual reproduction.
(ii) Genetic information – It switches on the genetic information for the development of gametes or gametophytes and switches off the sporophytic information. ‘
(iii) Maintenance of chromosome number – Meiosis maintains the fixed number of chromosomes in sexually reproducing organisms by halving the same. It is essential since the chromosome number becomes double after fertilisation.
(iv) Assortment of chromosomes – In meiosis paternal and maternal chromosomes assort independently. It causes reshuffling of chromosomes and the traits controlled by them. The variations help the breeders in improving the races of useful plants and animals.
(v) Crossing over – It introduces new combination of traits or variations.
(vi) Mutations – Chromosomal and genomic mutations can take place by irregularities of meiotic divisions. Some of these mutations are useful to the organism and are perpetuated by natural selection.
(vii) Evidence of basic relationship of organisms – Details of meiosis are essentially similar in the majority of organisms showing their basic similarity and relationship.

14. Discuss with your teacher about
(i) haploid insects and lower plants where cell division occurs, and
(ii)some haploid cells in higher plants where cell division does not occur.
Solnution:
(i) Cell division occurs in haploid insect, such as drones of honey bee and lower plant like gametophyte of algae, bryophytes, and pteridophytes.
(ii) Synergids and antipodals in embryo sac of ovule are haploid cells where cell division does not occur.

15. Can there be mitosis without DNA replication in’S’phase?
Solnution: No there cannot be any mitotic division without-DNA replication in ‘S’ phase.


Discussion

The relationship between r-AFS classification and pregnancy rate in patients receiving IVF treatment after laparoscopic surgery

The r-AFS classification depends on the results of laparoscopic examination and laparotomy. The staging of endometriosis requires the detailed observation and recording of the site, number, size, and depth of the endometriosis lesions, as well as the degree of adhesions, to define the final score. The r-AFS score is mainly used to assess disease severity and develop a post-operative treatment plan. The diameter of a ‘chocolate cyst’ in the ovary plays a critical role in determining the r-AFS score. For patients with endometriosis who want to become pregnant, this staging method has limited ability to predict future fertility after surgery [8]. Opoien et al. [20]conducted a large retrospective study of r-AFS classification of endometriosis and the success rate of using IVF/intracytoplasmic sperm injection in treating female infertility due to fallopian tube disease. They found that there was no difference in pregnancy rate or childbirth rate between patients with different stages of endometriosis or fallopian tube diseases after patients with adenomyoma were excluded. Similarly, the present study excluded patients with adenomyoma and only evaluated the outcome of IVF in the treatment of infertility due to fallopian tube disease. Our results show that there was no statistical difference between the implantation rate and the pregnancy rate in patients with different stages of endometriosis, consistent with the above study. In addition, the AUC ROC of r-AFS was 0.445, which was not significant for diagnosis. Therefore, our data suggest that the r-AFS classification can predict neither future pregnancy in endometriosis patients nor the outcome of IVF. We speculate that the EFI score maybe more sensitive in predicting pregnancy because it not only considers the size and number of lesions and the degree of local adhesion but also consider other reproductive factors, such as age, infertility duration, or fallopian tube and ovarian function.

The relationship between EFI score and pregnancy rate in patients receiving IVF treatment after laparoscopic surgery

In 2002, Fujushita et al. modified the AFS classification of endometriosis by adding the TOP score, (fallopian tubes, ovaries, peritoneum, and other factors) [21]. However, they did not consider the patient’s age or other factors affecting pregnancy. Adamson and Pasta (2010) further revised and updated the AFS classification system. They prospectively collected detailed clinical and surgical data of 579 patients with endometriosis and analysed 275 variables associated with pregnancy, thereby establishing the EFI. In addition, they confirmed that the EFI had a close correlation with pregnancy rate in 222 patients. In 2013, Tomassetti C et al. suggested that the EFI could be used clinically to counsel infertile endometriosis patients receiving reproductive surgery in specialized centers about their post-operative conception options [9]. However, their study did not include patients receiving IVF treatment after endometriosis surgery. We believed that in the course of ovarian stimulation for IVF treatment, it would be better to predict fertility after endometriosis surgery by comparing the dosage of medication, number of oocytes retrieved, embryo quality, implantation rate, and pregnancy rate in different groups of EFI scores. Unlike the r-AFS classification, the EFI objectively evaluates factors closely associated with female fertility, such as fallopian tube, tubal fimbria, and ovarian function. It incorporates the LF score which can evaluate the reproductive potential of pelvic organs and comprehensively includes several objective factors, such as patient’s age, duration of infertility, and pregnancy history. According to our data, the AUC ROC for embryo transfer during a fresh IVF cycle was only 0.641 using the EFI score. Patients with a score of 6 accounted for the largest proportion in our study. Patients with a score ≥6 had a significantly higher pregnancy rate than patients with a score ≤5. This is slightly different from the study of Adamson et al. According to their study, patients with a score of 7 accounted for the largest proportion [8]. Patients with scores of 8–10 had higher cumulative pregnancy rates than patients with scores of 5–7. A plausible explanation for this difference is that the participants in the two studies used different methods to conceive. The participants in our study were patients receiving IVF treatment after surgery. Therefore, the fallopian tube factors had little impact on the outcome of their IVF treatment, which could have lowered the cut-off point in the EFI in comparison to the patients who planned pregnancy naturally after the surgery.

The EFI incorporates patient age and duration of infertility. As shown in Table 2, no significant differences were observed in the baseline BMI and basal sex hormone levels between patients with EFI scores ≤5 and ≥6. The antral follicle count and the starting dose of Gn were different between the two groups (total Gn dose was also slightly different). This suggests that physicians estimated the starting Gn dose based on BMI, basal sex hormone levels, and antral follicle count in patients with different EFI scores. Therefore, both starting and total Gn doses were affected by oocyte reserve. The number of oocytes retrieved was also relatively higher in the ≥6 score group. However, although the rates of available embryos and top-quality embryos showed no significant differences between groups, the implantation rate and pregnancy rate were higher in the ≥6 score group, suggesting that a score of 6 can be considered an appropriate cut-off point when assessing EFI in endometriosis patients. The pregnancy rate was also higher in patients with score ≥6.

In summary, the EFI incorporates age and duration of infertility hence, it objectively evaluates the function of reproductive organs better than r-ASF. It has a relatively good predictive power for pregnancy outcomes for patients receiving IVF-ET treatment after laparoscopic surgery. The implantation rate and pregnancy rate were higher in patients with EFI score ≥6 than those with EFI score ≤5. These data provide an important reference to predict the post-operative pregnancy outcome for endometriosis patients, which is the most valuable conclusion of this study.

This study has several limitations. First, there were no significant differences in the rate of available embryos or the rate of top-quality embryos between EFI groups or between r-ASF groups. However, the implantation rate and pregnancy rate were significantly different between groups, suggesting that endometriosis can not only affect the ovaries and quality of oocytes but also the uterine endometrium for embryo implantation. A more convincing support of the implantation environment theory would be if we followed up the development of blastocysts by evaluating day 5 and day 6 blastocysts after implantation. Second, we used pregnancy/non-pregnancy as the relevant outcome to calculate the sample size without considering fertilisation or available embryos. Therefore, as shown in Table 3, the reason the r-AFS stage III-IV group had a low rate of polypronucleus zygotes and a high number of available embryos were that the r-AFS stage I-II group was relatively small. Third, this study failed to demonstrate whether starting an IVF cycle earlier after laparoscopic surgery can improve the specificity and sensitivity of the EFI. Fourth, severe uterine abnormalities, such as uterine fibroids, adversely affect pregnancy. However, the EFI does not incorporate such uterine conditions, a limitation of the scoring system. We acknowledge the impact of uterine conditions on pregnancy and the fact that EFI does not incorporate them. Therefore, to avoid any bias, we only included cases in this study that did not present with significant uterus fibroids as evaluated by laparoscopy and ultrasound. Finally, this was a retrospective study with the calculated cut-off EFI score of 6. Although the included sample size achieved the requirement for diagnostic tests, it will be necessary to conduct randomised, prospective studies with large numbers of patients to validate and evaluate the EFI and its cut-off point. It is better to analyse pregnancy probability in each stage of the EFI with a larger sample size.


Contents

Pain and infertility are common symptoms, although 20–25% of women are asymptomatic. [1]

Pelvic pain Edit

A major symptom of endometriosis is recurring pelvic pain. The pain can range from mild to severe cramping or stabbing pain that occurs on both sides of the pelvis, in the lower back and rectal area, and even down the legs. The amount of pain a person feels correlates weakly with the extent or stage (1 through 4) of endometriosis, with some individuals having little or no pain despite having extensive endometriosis or endometriosis with scarring, while others may have severe pain even though they have only a few small areas of endometriosis. [16] The most severe pain is typically associated with menstruation. Pain can also start a week before a menstrual period, during and even a week after a menstrual period, or it can be constant. The pain can be debilitating and result in emotional stress. [17] Symptoms of endometriosis-related pain may include:

    (64%) [18] – painful, sometimes disabling cramps during the menstrual period pain may get worse over time (progressive pain), also lower back pains linked to the pelvis – typically accompanied by lower back pain or abdominal pain – painful sexual intercourse – urinary urgency, frequency, and sometimes painful voiding [19] – pain associated with ovulation [20]
  • bodily movement pain – present during exercise, standing, or walking [19]

Compared with patients with superficial endometriosis, those with deep disease appear to be more likely to report shooting rectal pain and a sense of their insides being pulled down. [21] Individual pain areas and pain intensity appear to be unrelated to the surgical diagnosis, and the area of pain unrelated to the area of endometriosis. [21]

There are multiple causes of pain. Endometriosis lesions react to hormonal stimulation and may "bleed" at the time of menstruation. The blood accumulates locally if it is not cleared shortly by the immune, circulatory, and lymphatic system. This may further lead to swelling, which triggers inflammation with the activation of cytokines, which results in pain. Another source of pain is the organ dislocation that arises from adhesion binding internal organs to each other. The ovaries, the uterus, the oviducts, the peritoneum, and the bladder can be bound together. Pain triggered in this way can last throughout the menstrual cycle, not just during menstrual periods. [22]

Also, endometriotic lesions can develop their own nerve supply, thereby creating a direct and two-way interaction between lesions and the central nervous system, potentially producing a variety of individual differences in pain that can, in some cases, become independent of the disease itself. [16] Nerve fibres and blood vessels are thought to grow into endometriosis lesions by a process known as neuroangiogenesis. [23]

Infertility Edit

About a third of women with infertility have endometriosis. [1] Among those with endometriosis, about 40% are infertile. [1] The pathogenesis of infertility is dependent on the stage of disease: in early stage disease, it is hypothesised that this is secondary to an inflammatory response that impairs various aspects of conception, whereas in later stage disease distorted pelvic anatomy and adhesions contribute to impaired fertilisation. [24]

Other Edit

Other symptoms include diarrhea or constipation, chronic fatigue, nausea and vomiting, migraines, low-grade fevers, heavy (44%) and/or irregular periods (60%), and hypoglycemia. [18] [25] [26] [19] There is an association between endometriosis and certain types of cancers, notably some types of ovarian cancer, [27] [28] non-Hodgkin's lymphoma and brain cancer. [29] Endometriosis is unrelated to endometrial cancer. [30] Rarely, endometriosis can cause endometrium-like tissue to be found in other parts of the body. Thoracic endometriosis occurs when endometrium-like tissue implants in the lungs or pleura. Manifestations of this include coughing up blood, a collapsed lung, or bleeding into the pleural space. [10] [31]

Stress may be a cause or a consequence of endometriosis. [32]

Complications Edit

Complications of endometriosis include internal scarring, adhesions, pelvic cysts, chocolate cysts of ovaries, ruptured cysts, and bowel and ureter obstruction resulting from pelvic adhesions. [33] Endometriosis-associated infertility can be related to scar formation and anatomical distortions due to the endometriosis. [2]

Ovarian endometriosis may complicate pregnancy by decidualization, abscess and/or rupture. [34]

Thoracic endometriosis can be associated with recurrent thoracic endometriosis syndrome at times of a menstrual period that includes catamenial pneumothorax in 73% of women, catamenial hemothorax in 14%, catamenial hemoptysis in 7%, and pulmonary nodules in 6%. [35] [36]

A 20-year study of 12,000 women with endometriosis found that individuals under 40 who are diagnosed with endometriosis are 3 times more likely to have heart problems than their healthy peers. [37] [38]

It results in few deaths with unadjusted and age-standardized death rates of 0.1 and 0.0 per 100,000. [4]

Genetics Edit

Endometriosis is a heritable condition that is influenced by both genetic and environmental factors. [39] Children or siblings of people with endometriosis are at higher risk of developing endometriosis themselves low progesterone levels may be genetic, and may contribute to a hormone imbalance. [40] There is an approximate six-fold increased incidence in individuals with an affected first-degree relative. [41]

It has been proposed that endometriosis results from a series of multiple hits within target genes, in a mechanism similar to the development of cancer. [39] In this case, the initial mutation may be either somatic or heritable. [39]

Individual genomic changes (found by genotyping including genome-wide association studies) that have been associated with endometriosis include: [42] [43] [44]

Chromosome Gene/Region of Mutation Gene Product Function
1 WNT4 Wingless-type MMTV integration site family member 4 Vital for development of the female reproductive organs
2 GREB1/FN1 Growth regulation by estrogen in breast cancer 1/Fibronectin 1 Early response gene in the estrogen regulation pathway/Cell adhesion and migration processes
6 ID4 Inhibitor of DNA binding 4 Ovarian oncogene, biological function unknown
7 7p15.2 Transcription factors Influence transcriptional regulation of uterine development
9 CDKN2BAS Cyclin-dependent kinase inhibitor 2B antisense RNA Regulation of tumour suppressor genes
10 10q26
12 VEZT Vezatin, an adherens junction transmembrane protein Tumor suppressor gene
19 MUC16 (CA-125) Mucin 16, cell surface associated Form protective mucous barriers

There are many findings of altered gene expression and epigenetics, but both of these can also be a secondary result of, for example, environmental factors and altered metabolism. Examples of altered gene expression include that of miRNAs. [39]

Environmental toxins Edit

Some factors associated with endometriosis include:

  • prolonged exposure to estrogen for example, in late menopause [45] or early menarche [46][47]
  • obstruction of menstrual outflow for example, in Müllerian anomalies [45]

Several studies have investigated the potential link between exposure to dioxins and endometriosis, but the evidence is equivocal and potential mechanisms are poorly understood. [48] A 2004 review of studies of dioxin and endometriosis concluded that "the human data supporting the dioxin-endometriosis association are scanty and conflicting", [49] and a 2009 follow-up review also found that there was "insufficient evidence" in support of a link between dioxin exposure and developing endometriosis. [50] A 2008 review concluded that more work was needed, stating that "although preliminary work suggests a potential involvement of exposure to dioxins in the pathogenesis of endometriosis, much work remains to clearly define cause and effect and to understand the potential mechanism of toxicity". [51]

While the exact cause of endometriosis remains unknown, many theories have been presented to better understand and explain its development. These concepts do not necessarily exclude each other. The pathophysiology of endometriosis is likely to be multifactorial and to involve an interplay between several factors. [39]

Formation Edit

The main theories for the formation of the ectopic endometrium-like tissue include retrograde menstruation, Müllerianosis, coelomic metaplasia, vascular dissemination of stem cells, and surgical transplantation were postulated as early as 1870. Each is further described below. [10] [52] [53]

Retrograde menstruation theory Edit

The theory of retrograde menstruation (also called the implantation theory or transplantation theory) is the most commonly accepted theory for the dissemination and transformation of ectopic endometrium into endometriosis. It suggests that during a woman's menstrual flow, some of the endometrial debris flow backward through the Fallopian tubes and into the peritoneal cavity, attaching itself to the peritoneal surface (the lining of the abdominal cavity) where it can proceed to invade the tissue as or transform into endometriosis. It is not clear at what stage the transformation of endometrium, or any cell of origin such as stem cells or coelomic cells (see those theories below), to endometriosis begins. [39] [52] [54]

Retrograde menstruation alone is not able to explain all instances of endometriosis, and additional factors such as genetics, immunology, stem cell migration, and coelomic metaplasia (see "Other theories" on this page) are needed to account for disseminated disease and why many individuals with retrograde menstruation are not diagnosed with endometriosis. In addition, endometriosis has shown up in people who have never experienced menstruation including cisgender men, [55] fetuses, [56] and prepubescent girls. [57] [58] Further theoretical additions are needed to compliment the retrograde menstruation theory to explain why cases of endometriosis show up in the brain [59] and lungs. [60] This theory has numerous other associated issues. [61]

Researchers are investigating the possibility that the immune system may not be able to cope with the cyclic onslaught of retrograde menstrual fluid. In this context there is interest in studying the relationship of endometriosis to autoimmune disease, allergic reactions, and the impact of toxic materials. [62] [63] It is still unclear what, if any, causal relationship exists between toxic materials or autoimmune disease and endometriosis. There are immune system changes in people with endometriosis, such as an increase of macrophage-derived secretion products, but it is unknown if these are contributing to the disorder or are reactions from it. [64]

Endometriotic lesions differ in their biochemistry, hormonal response, immunology, inflammatory response when compared to endometrium. [65] [10] This is likely because the cells that give rise to endometriosis are a side population of cells. [39] Similarly, there are changes in, for example, the mesothelium of the peritoneum in people with endometriosis, such as loss of tight junctions, but it is unknown if these are causes or effects of the disorder. [64]

In rare cases where imperforate hymen does not resolve itself prior to the first menstrual cycle and goes undetected, blood and endometrium are trapped within the uterus until such time as the problem is resolved by surgical incision. Many health care practitioners never encounter this defect, and due to the flu-like symptoms it is often misdiagnosed or overlooked until multiple menstrual cycles have passed. By the time a correct diagnosis has been made, endometrium and other fluids have filled the uterus and Fallopian tubes with results similar to retrograde menstruation resulting in endometriosis. The initial stage of endometriosis may vary based on the time elapsed between onset and surgical procedure. [ citation needed ]

The theory of retrograde menstruation as a cause of endometriosis was first proposed by John A. Sampson. [52] [66]

Other theories Edit

  • Stem cells: Endometriosis may arise from stem cells from bone marrow and potentially other sources. In particular, this theory explains endometriosis found in areas remote from the pelvis such as the brain or lungs. [53]Stem cells may be from local cells such as the peritoneum (see coelomic metaplasia below) or cells disseminated in the blood stream (see vascular dissemination below) such as those from the bone marrow. [52][53][67]
  • Vascular dissemination: Vascular dissemination is a 1927 theory that has been revived with new studies of bone-marrow stem cells involved in pathogenesis. [53][67]
  • Environment: Environmental toxins (e.g., dioxin, nickel) may cause endometriosis. [68][69]
  • Müllerianosis: A theory supported by foetal autopsy is that cells with the potential to become endometrial, which are laid down in tracts during embryonic development called the female reproductive (Müllerian) tract as it migrates downward at 8–10 weeks of embryonic life, could become dislocated from the migrating uterus and act like seeds or stem cells. [52][56]
  • Coelomic metaplasia: Coelomic cells which are the common ancestor of endometrial and peritoneal cells may undergo metaplasia (transformation) from one type of cell to the other, perhaps triggered by inflammation. [52][70]
  • Vasculogenesis: Up to 37% of the microvascular endothelium of ectopic endometrial tissue originates from endothelial progenitor cells, which result in de novo formation of microvessels by the process of vasculogenesis rather than the conventional process of angiogenesis. [71] [clarification needed]
  • Neural growth: An increased expression of new nerve fibres is found in endometriosis but does not fully explain the formation of ectopic endometriotic tissue and is not definitely correlated with the amount of perceived pain. [72] [clarification needed]
  • Autoimmune: Graves disease is an autoimmune disease characterized by hyperthyroidism, goiter, ophthalmopathy, and dermopathy. People with endometriosis had higher rates of Graves disease. One of these potential links between Graves disease and endometriosis is autoimmunity. [73][74] : Influx of iron is associated with the local destruction of the peritoneal mesothelium, leading to the adhesion of ectopic endometriotic cells. [75] Peritoneal iron overload has been suggested to be caused by the destruction of erythrocytes, which contain the iron-binding protein hemoglobin, or a deficiency in the peritoneal iron metabolism system.[75] Oxidative stress activity and reactive oxygen species (such as superoxide anions and peroxide levels) are reported to be higher than normal in people with endometriosis. [75] Oxidative stress and the presence of excess ROS can damage tissue and induce rapid cellular division. [75] Mechanistically, there are several cellular pathways by which oxidative stress may lead to or may induce proliferation of endometriotic lesions, including the mitogen activated protein (MAP) kinase pathway and the extracellular signal-related kinase (ERK) pathway. [75] Activation of both of the MAP and ERK pathways lead to increased levels of c-Fos and c-Jun, which are proto-oncogenes that are associated with high-grade lesions. [75]

Localization Edit

Most often, endometriosis is found on the:

Less common pelvic sites are:

Endometriosis may spread to the cervix and vagina or to sites of a surgical abdominal incision, known as "scar endometriosis." [76] Rectovaginal or bowel endometriosis affects approximately 5-12% of those with endometriosis, and can cause severe pain with bowel movements. [77] [ citation needed ]

Extrapelvic endometriosis Edit

Rarely, endometriosis appears in extrapelvic parts of the body, such as the lungs, brain, and skin. [2] [36] [76] "Scar endometriosis" can occur in surgical abdominal incisions. [76] Risk factors for scar endometriosis include previous abdominal surgeries, such as a hysterotomy or cesarean section, or ectopic pregnancies, salpingostomy puerperal sterilization, laparoscopy, amniocentesis, appendectomy, episiotomy, vaginal hysterectomies, and hernia repair. [78] [79] [80]

Endometriosis may also present with skin lesions in cutaneous endometriosis. [76]

Less commonly lesions can be found on the diaphragm or lungs. Diaphragmatic endometriosis is rare, almost always on the right hemidiaphragm, and may inflict the cyclic pain of the right scapula (shoulder) or cervical area (neck) during a menstrual period. [81] Pulmonary endometriosis can be associated with a thoracic endometriosis syndrome that can include catamenial (occurs during menstruation) pneumothorax seen in 73% of women with the syndrome, catamenial hemothorax in 14%, catamenial hemoptysis in 7%, and pulmonary nodules in 6%. [36]

A health history and a physical examination can lead the health care practitioner to suspect endometriosis. The potential benefits or harms related to any combination of non-invasive diagnostic tests for endometriosis are not clear (there is insufficient research) compared to the 'gold standard' of undergoing diagnostic surgery and adding a biopsy (as 1/2 of laparoscopic diagnostic try is a false positive [82] ). [83]

In the UK, there is an average of 7.5 years between an individual first seeing a doctor about their symptoms and receiving a firm diagnosis. [84]

The most common sites of endometriosis are the ovaries, followed by the Douglas pouch, the posterior leaves of the broad ligaments, and the sacrouterine ligaments. [18]

Laparoscopy Edit

Laparoscopy, a surgical procedure where a camera is used to look inside the abdominal cavity, is the only way to accurately diagnose the extent and severity of pelvic/abdominal endometriosis. [85] Laparoscopy is not an applicable test for extrapelvic sites such as umbilicus, hernia sacs, abdominal wall, lung, or kidneys. [85]

Reviews in 2019 and 2020 concluded that 1) with advances in imaging, endometriosis diagnosis should no longer be considered synonymous with immediate laparoscopy for diagnosis, and 2) endometriosis should be classified a syndrome that requires confirmation of visible lesions seen at laparoscopy in addition to characteristic symptoms. [86] [87]

Laparoscopy permits lesion visualization unless the lesion is visible externally (e.g., an endometriotic nodule in the vagina) or is extra-abdominal. [85] If the growths (lesions) are not visible, a biopsy must be taken to determine the diagnosis. [82] Surgery for diagnoses also allows for surgical treatment of endometriosis at the same time.

During a laparoscopic procedure lesions can appear dark blue, powder-burn black, red, white, yellow, brown or non-pigmented. Lesions vary in size. [88] Some within the pelvis walls may not be visible, as normal-appearing peritoneum of infertile women reveals endometriosis on biopsy in 6–13% of cases. [89] Early endometriosis typically occurs on the surfaces of organs in the pelvic and intra-abdominal areas. [88] Health care providers may call areas of endometriosis by different names, such as implants, lesions, or nodules. Larger lesions may be seen within the ovaries as endometriomas or "chocolate cysts", "chocolate" because they contain a thick brownish fluid, mostly old blood. [88]

Frequently during diagnostic laparoscopy, no lesions are found in individuals with chronic pelvic pain, a symptom common to other disorders including adenomyosis, pelvic adhesions, pelvic inflammatory disease, congenital anomalies of the reproductive tract, and ovarian or tubal masses. [90]

Ultrasound Edit

The use of pelvic ultrasound may identify large endometriotic cysts (called endometriomas). However, smaller endometriosis implants cannot be visualized with ultrasound technique. [91]

Vaginal ultrasound has a clinical value in the diagnosis of endometrioma and before operating for deep endometriosis. [92] This applies to the identification of the spread of disease in individuals with well-established clinical suspicion of endometriosis. [92] Vaginal ultrasound is inexpensive, easily accessible, has no contraindications and requires no preparation. [92] Healthcare professionals conducting ultrasound examinations need to be experienced. [92] By extending the ultrasound assessment into the posterior and anterior pelvic compartments the sonographer is able to evaluate structural mobility and look for deep infiltrating endometriotic nodules noting the size, location and distance from the anus if applicable. [93] An improvement in sonographic detection of deep infiltrating endometriosis will not only reduce the number of diagnostic laparoscopies, it will guide management and enhance quality of life. [93]

Magnetic resonance imaging Edit

Use of MRI is another method to detect lesions in a non-invasive manner. [85] MRI is not widely used due to its cost and limited availability, however, it has the ability to detect the most common form of endometriosis (endometrioma) with a sufficient accuracy. [85] It is recommended for the patient to receive an anti-spasmodic agent (hyoscine butylbromide for example), a big glass of water (if bladder is empty), to undergo MRI scanning in supine position and applying abdominal strap for having a better image quality from the MRI. [94]

Phased coil arrays are also recommended. [94]

Sequences Edit

T1W with and without suppression of fat is recommended for endometriomas meanwhile, sagittal, axial and oblique 2D T2W are recommended for deep infiltrating endometriosis. [94]

Staging Edit

Surgically, endometriosis can be staged I–IV by the revised classification of the American Society of Reproductive Medicine from 1997. [95] The process is a complex point system that assesses lesions and adhesions in the pelvic organs, but it is important to note staging assesses physical disease only, not the level of pain or infertility. A person with Stage I endometriosis may have a little disease and severe pain, while a person with Stage IV endometriosis may have severe disease and no pain or vice versa. In principle the various stages show these findings: [96]

Findings restricted to only superficial lesions and possibly a few filmy adhesions.

In addition, some deep lesions are present in the cul-de-sac.

As above, plus the presence of endometriomas on the ovary and more adhesions.

As above, plus large endometriomas, extensive adhesions.

Markers Edit

An area of research is the search for endometriosis markers. [97]

In 2010, essentially all proposed biomarkers for endometriosis were of unclear medical use, although some appear to be promising. [97] The one biomarker that has been in use over the last 20 years is CA-125. [97] A 2016 review found that this biomarker was present in those with symptoms of endometriosis and, once ovarian cancer has been ruled out, a positive CA-125 may confirm the diagnosis. [98] Its performance in ruling out endometriosis is low. [98] CA-125 levels appear to fall during endometriosis treatment, but it has not shown a correlation with disease response. [97]

Another review in 2011 identified several putative biomarkers upon biopsy, including findings of small sensory nerve fibers or defectively expressed β3 integrin subunit. [99] It has been postulated a future diagnostic tool for endometriosis will consist of a panel of several specific and sensitive biomarkers, including both substance concentrations and genetic predisposition. [97]

A 2016 review of endometrial biomarkers for diagnosing endometriosis was unable to draw conclusions due to the low quality of the evidence. [100]

MicroRNAs have the potential to be used in diagnostic and therapeutic decisions [101]

Histopathology Edit

For a histopathological diagnosis, at least two of the following three criteria should be present: [102]

  • Endometrial type stroma
  • Endometrial epithelium with glands
  • Evidence of chronic hemorrhage, mainly hemosiderin deposits

Immunohistochemistry has been found to be useful in diagnosing endometriosis as stromal cells have a peculiar surface antigen, CD10, thus allowing the pathologist go straight to a staining area and hence confirm the presence of stromal cells and sometimes glandular tissue is thus identified that was missed on routine H&E staining. [103] [ better source needed ]

Endometriosis, abdominal wall

Micrograph showing endometriosis (right) and ovarian stroma (left)

Micrograph of the wall of an endometrioma. All features of endometriosis are present (endometrial glands, endometrial stroma and hemosiderin-laden macrophages).

Pain quantification Edit

The most common pain scale for quantification of endometriosis-related pain is the visual analogue scale (VAS) VAS and numerical rating scale (NRS) were the best adapted pain scales for pain measurement in endometriosis. For research purposes, and for more detailed pain measurement in clinical practice, VAS or NRS for each type of typical pain related to endometriosis (dysmenorrhea, deep dyspareunia and non-menstrual chronic pelvic pain), combined with the clinical global impression (CGI) and a quality of life scale, are used. [104]

Limited evidence indicates that the use of combined oral contraceptives is associated with a reduced risk of endometriosis, as is regular exercise and the avoidance of alcohol and caffeine. [2] [12]

While there is no cure for endometriosis, there are two types of interventions treatment of pain and treatment of endometriosis-associated infertility. [105] In many cases, menopause (natural or surgical) will abate the process. [106] In the reproductive years, endometriosis is merely managed: the goal is to provide pain relief, to restrict progression of the process, and to restore or preserve fertility where needed. In younger individuals, surgical treatment attempts to remove endometriotic tissue and preserve the ovaries without damaging normal tissue. [10] [107]

In general, the diagnosis of endometriosis is confirmed during surgery, at which time ablative steps can be taken. Further steps depend on circumstances: someone without infertility can manage symptoms with pain medication and hormonal medication that suppresses the natural cycle, while an infertile individual may be treated expectantly after surgery, with fertility medication, or with IVF. As to the surgical procedure, ablation (or fulguration) of endometriosis (burning and vaporizing the lesions with an electric device) has shown a high rate of short-term recurrence after the procedure. The best surgical procedure with much lower rate of short-term recurrence is to excise (cut and remove) the lesions completely. [108]

Surgery Edit

Surgery, if done, should generally be performed laparoscopically (through keyhole surgery) rather than open. [82] Treatment consists of the ablation or excision of the endometriosis, electrocoagulation, [109] lysis of adhesions, resection of endometriomas, and restoration of normal pelvic anatomy as much as is possible. [82] [110] When laparoscopic surgery is used, small instruments are inserted through the incisions to remove the endometriosis tissue and adhesions. Because the incisions are very small, there will only be small scars on the skin after the procedure, and most individuals recover from surgery quickly and have a reduced risk of adhesions. [111]

As for deep endometriosis, a segmental resection or shaving of nodules is effective but is associated with an important rate of complications which about 4,6% is major. [112]

Historically, a hysterectomy (removal of the uterus) was thought to be a cure for endometriosis in individuals who do not wish to conceive. Removal of the uterus may be beneficial as part of the treatment, if the uterus itself is affected by adenomyosis. However, this should only be done in combination with removal of the endometriosis by excision. If endometriosis is not also removed at the time of hysterectomy, pain may persist. [82]

Presacral neurectomy may be performed where the nerves to the uterus are cut. However, this technique is not usually used due to the high incidence of associated complications including presacral hematoma and irreversible problems with urination and constipation. [82]

Risks and safety of pelvic surgery Edit

Risk of developing complications following surgery depend on the type of the lesion that has undergone surgery. [109] 55% to 100% of individuals develop adhesions following pelvic surgery, [113] which can result in infertility, chronic abdominal and pelvic pain, and difficult reoperative surgery. Trehan's temporary ovarian suspension, a technique in which the ovaries are suspended for a week after surgery, may be used to reduce the incidence of adhesions after endometriosis surgery. [114] [115] Removal of cysts on the ovary without removing the ovary is a safe procedure. [109]

Hormonal medications Edit

    therapy: Birth control pills reduce the menstrual pain and recurrence rate for endometrioma following conservative surgery for endometriosis. [116] : Progesterone counteracts estrogen and inhibits the growth of the endometrium. [117] (Danocrine) and gestrinone (Dimetrose, Nemestran) are suppressive steroids with some androgenic activity. [107] Both agents inhibit the growth of endometriosis but their use has declined, due in part to virilizing side effects such as excessive hair growth and voice changes. [118] : These drugs include GnRH agonists such as leuprorelin (Lupron) and GnRH antagonists such as elagolix (Orilissa) and are thought to work by decreasing estrogen levels. [119] A 2010 Cochrane review found that GnRH modulators were more effective for pain relief in endometriosis than no treatment or placebo, but were not more effective than danazol or intrauterine progestogen, and had more side effects than danazol. [119] A 2018 Swedish systematic review found that GnRH modulators had similar pain-relieving effects to gestagen, but also decreased bone density. [92] are medications that block the formation of estrogen and have become of interest for researchers who are treating endometriosis. [120] Examples of aromatase inhibitors include anastrozole and letrozole. Evidence for aromatase inhibitors is limited due to the limited number and quality of studies available, though show promising benefit in terms of pain control. [121]

Other medication Edit

    : Anti-inflammatory. They are commonly used in conjunction with other therapy. Examples of over-the-counter NSAIDs include ibuprofen and naproxen. [122] Ibuprofen and naproxen are combined COX-1 and COX-2 inhibitors. COX-2 selective agents such as celecoxib have a more limited gastrointestinal toxicity. [123] NSAID injections of ketorolac can be helpful for severe pain or if stomach pain prevents oral NSAID use. For more severe cases narcotic prescription drugs may be used. : Morphine sulphate tablets and other opioid painkillers work by mimicking the action of naturally occurring pain-reducing chemicals called "endorphins". There are different long acting and short acting medications that can be used alone or in combination to provide appropriate pain control. was reported to have comparable benefits to gestrinone and danazol in patients who had had laparoscopic surgery, though the review notes that the two trials were small and of "poor methodological quality" and results should be "interpreted cautiously" as better quality research is needed. [124] , an immunomodulating agent, has been theorized to improve pain as well as improve pregnancy rates in individuals with endometriosis. A 2012 Cochrane review found that there was not enough evidence to support the effectiveness or safety of either of these uses. [125] Current American Congress of Obstetricians and Gynecologists (ACOG) guidelines do not include immunomodulators, such as pentoxifylline, in standard treatment protocols. [126] lack clinical evidence of efficacy in endometriosis therapy. [127] Under experimental in vitro and in vivo conditions, compounds that have been shown to exert inhibitory effects on endometriotic lesions include growth factor inhibitors, endogenous angiogenesis inhibitors, fumagillin analogues, statins, cyclo-oxygenase-2 inhibitors, phytochemical compounds, immunomodulators, dopamine agonists, peroxisome proliferator-activated receptor agonists, progestins, danazol and gonadotropin-releasing hormone agonists. [127] However, many of these agents are associated with undesirable side effects and more research is necessary. An ideal therapy would diminish inflammation and underlying symptoms without being contraceptive. [128][129]

The overall effectiveness of manual physical therapy to treat endometriosis has not yet been identified. [130]

Comparison of interventions Edit

Medicinal and surgical interventions produce roughly equivalent pain-relief benefits. Recurrence of pain was found to be 44 and 53 percent with medicinal and surgical interventions, respectively. [40] Each approach has advantages and disadvantages. [70]

As of 2013 [update] evidence on how effective medication is for relieving pain associated with endometriosis was limited. [105] A 2018 Swedish systematic review found a large number of studies but a general lack of scientific evidence for most treatments. [92] There was only one study of sufficient quality and relevance comparing the effect of surgery and non-surgery. [131] Cohort studies indicate that surgery is effective in decreasing pain. [131] Most complications occurred in cases of low intestinal anastomosis, while risk of fistula occurred in cases of combined abdominal or vaginal surgery, and urinary tract problems were common in intestinal surgery. [131] The evidence was found to be insufficient regarding surgical intervention. [131]

The advantages of surgery are demonstrated efficacy for pain control, [132] it is more effective for infertility than medicinal intervention, [107] it provides a definitive diagnosis, [107] and surgery can often be performed as a minimally invasive (laparoscopic) procedure to reduce morbidity and minimize the risk of post-operative adhesions. [133] Efforts to develop effective strategies to reduce or prevent adhesions have been undertaken, but their formation remain a frequent side effect of abdominal surgery. [113]

The advantages of physical therapy techniques are decreased cost, absence of major side-effects, it does not interfere with fertility, and near-universal increase of sexual function. [134] Disadvantages are that there are no large or long-term studies of its use for treating pain or infertility related to endometriosis. [134]

Treatment of infertility Edit

Surgery is more effective than medicinal intervention for addressing infertility associated with endometriosis. [107] Surgery attempts to remove endometrium-like tissue [10] and preserve the ovaries without damaging normal tissue. [107] Receiving hormonal suppression therapy after surgery might be positive regarding endometriosis recurrence and pregnancy. [135] In-vitro fertilization (IVF) procedures are effective in improving fertility in many individuals with endometriosis. [136]

During fertility treatment, the ultralong pretreatment with GnRH-agonist has a higher chance of resulting in pregnancy for individuals with endometriosis, compared to the short pretreatment. [92]

The underlying process that causes endometriosis may not cease after a surgical or medical intervention. A study has shown that dysmenorrhea recurs at a rate of 30 percent within a year following laparoscopic surgery. Resurgence of lesions tend to appear in the same location if the lesions were not completely removed during surgery. It has been shown that laser ablation resulted in higher and earlier recurrence rates when compared with endometrioma cystectomy and recurrence after repetitive laparoscopy was similar to that after the first surgery. Endometriosis can come back after hysterectomy and bilateral salpingo-oophorectomy. It has 10% recurrent rate. [137]

Endometriosis recurrence following conservative surgery is estimated as 21.5% at 2 years and 40-50% at 5 years. [138]

Determining how many people have endometriosis is challenging because definitive diagnosis requires surgical visualization. [14] Criteria that are commonly used to establish a diagnosis include pelvic pain, infertility, surgical assessment, and in some cases, magnetic resonance imaging. These studies suggest that endometriosis affects approximately 11% of women in the general population. [14] [2] Endometriosis is most common in those in their thirties and forties however, it can begin as early as 8 years old. [2] [3]

It chiefly affects adults from premenarche to postmenopause, regardless of race or ethnicity or whether or not they have had children. It is primarily a disease of the reproductive years. [139] Incidences of endometriosis have occurred in postmenopausal individuals, [140] and in less common cases, individuals may have had endometriosis symptoms before they even reach menarche. [141] [58]

The rate of recurrence of endometriosis is estimated to be 40-50% for adults over a 5-year period. [142] The rate of recurrence has been shown to increase with time from surgery and is not associated with the stage of the disease, initial site, surgical method used, or post-surgical treatment. [142]

Endometriosis was first discovered microscopically by Karl von Rokitansky in 1860, [143] although the earliest antecedents may have stemmed from concepts published almost 4,000 years ago. [144] The Hippocratic Corpus outlines symptoms similar to endometriosis, including uterine ulcers, adhesions, and infertility. [144] Historically, women with these symptoms were treated with leeches, straitjackets, bloodletting, chemical douches, genital mutilation, pregnancy (as a form of treatment), hanging upside down, surgical intervention, and even killing due to suspicion of demonic possession. [144] Hippocratic doctors recognized and treated chronic pelvic pain as a true organic disorder 2,500 years ago, but during the Middle Ages, there was a shift into believing that women with pelvic pain were mad, immoral, imagining the pain, or simply misbehaving. [144] The symptoms of inexplicable chronic pelvic pain were often attributed to imagined madness, female weakness, promiscuity, or hysteria. [144] The historical diagnosis of hysteria, which was thought to be a psychological disease, may have indeed been endometriosis. [144] The idea that chronic pelvic pain was related to mental illness influenced modern attitudes regarding individuals with endometriosis, leading to delays in correct diagnosis and indifference to the patients' true pain throughout the 20th and into the 21st century. [144]

Hippocratic doctors believed that delaying childbearing could trigger diseases of the uterus, which caused endometriosis-like symptoms. Women with dysmenorrhea were encouraged to marry and have children at a young age. [144] The fact that Hippocratics were recommending changes in marriage practices due to an endometriosis-like illness implies that this disease was likely common, with rates higher than the 5-15% prevalence that is often cited today. [144] If indeed this disorder was so common historically, this may point away from modern theories that suggest links between endometriosis and dioxins, PCBs, and chemicals. [144]

The early treatment of endometriosis was surgical and included oophorectomy (removal of the ovaries) and hysterectomy (removal of the uterus). [145] In the 1940s, the only available hormonal therapies for endometriosis were high-dose testosterone and high-dose estrogen therapy. [146] High-dose estrogen therapy with diethylstilbestrol for endometriosis was first reported by Karnaky in 1948 and was the main pharmacological treatment for the condition in the early 1950s. [147] [148] [149] Pseudopregnancy (high-dose estrogen–progestogen therapy) for endometriosis was first described by Kistner in the late 1950s. [147] [148] Pseudopregnancy as well as progestogen monotherapy dominated the treatment of endometriosis in the 1960s and 1970s. [149] These agents, although efficacious, were associated with intolerable side effects. Danazol was first described for endometriosis in 1971 and became the main therapy in the 1970s and 1980s. [147] [148] [149] In the 1980s GnRH agonists gained prominence for the treatment of endometriosis and by the 1990s had become the most widely used therapy. [148] [149] Oral GnRH antagonists such as elagolix were introduced for the treatment of endometriosis in 2018. [150]

Public figures Edit

A number of public figures have spoken about their experience with endometriosis, including:

Economic burden Edit

The economic burden of endometriosis is widespread and multifaceted. [159] Endometriosis is a chronic disease that has direct and indirect costs which include loss of work days, direct costs of treatment, symptom management, and treatment of other associated conditions such as depression or chronic pain. [159] One factor which seems to be associated with especially high costs is the delay between onset of symptoms and diagnosis. Costs vary greatly between countries. [160]

Medical culture Edit

There are a number of barriers that those affected face to receiving diagnosis and treatment for endometriosis. Some of these include outdated standards for laparoscopic evaluation, stigma about discussing menstruation and sex, lack of understanding of the disease, primary care physicians lack of knowledge, and assumptions about typical menstrual pain. [161] On average, those later diagnosed with endometriosis waited 2.3 years after the onset of symptoms before seeking treatment and nearly three quarters of women receive a misdiagnosis prior to endometriosis. [162] Self-help groups say practitioners delay making the diagnosis, often because they do not consider it a possibility. There is a typical delay of 7–12 years from symptom onset in affected individuals to professional diagnosis. [163] There is a general lack of knowledge about endometriosis among primary care physicians. Half of general health care providers surveyed in a 2013 study were unable to name three symptoms of endometriosis. [164] Health care providers are also likely to dismiss described symptoms as normal menstruation. [165] Younger patients may also feel uncomfortable discussing symptoms with a physician. [165]

Race and Ethnicity Edit

Race and ethnicity may play a role in how endometriosis affects one's life. Endometriosis is less thoroughly studied among Black people, and the research that has been done is outdated. [166] Black people with endometriosis may face barriers in receiving care due to misconceptions about how Black people feel pain. [167] Since pain is the primary symptom of endometriosis, this makes it increasingly possible for doctors to dismiss pain symptoms when their patient is Black. [168] [167] An inaccurate diagnosis is also more likely since Black women are at a higher risk for other related conditions such as uterine fibroids. [168]

Cultural differences among ethnic groups also contribute to attitudes toward and treatment of endometriosis, especially in Hispanic or Latino communities. A study done in Puerto Rico in 2020 found that health care and interactions with friends and family related to discussing endometriosis were affected by stigma. [169] The most common finding was a referral to those expressing pain related to endometriosis as “changuerıa” or "changas", terms used in Puerto Rico to describe pointless whining and complaining, often directed at children. [169]

  1. ^ abcdefghijklmnop Bulletti C, Coccia ME, Battistoni S, Borini A (August 2010). "Endometriosis and infertility". Journal of Assisted Reproduction and Genetics. 27 (8): 441–7. doi:10.1007/s10815-010-9436-1. PMC2941592 . PMID20574791.
  2. ^ abcdefghijklmnopqrstuvwxyz
  3. "Endometriosis". womenshealth.gov. 13 February 2017. Archived from the original on 13 May 2017 . Retrieved 20 May 2017 .
  4. ^ abc
  5. McGrath PJ, Stevens BJ, Walker SM, Zempsky WT (2013). Oxford Textbook of Paediatric Pain. OUP Oxford. p. 300. ISBN9780199642656 . Archived from the original on 2017-09-10.
  6. ^ abcde
  7. GBD 2015 Disease and Injury Incidence and Prevalence Collaborators (October 2016). "Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1545–1602. doi: 10.1016/S0140-6736(16)31678-6 . PMC5055577 . PMID27733282. CS1 maint: uses authors parameter (link)
  8. ^
  9. Wang, Haidong Naghavi, Mohsen Allen, Christine Barber, Ryan M. Bhutta, Zulfiqar A. Carter, Austin Casey, Daniel C. Charlson, Fiona J. Chen, Alan Zian Coates, Matthew M. Coggeshall, Megan Dandona, Lalit Dicker, Daniel J. Erskine, Holly E. Ferrari, Alize J. Fitzmaurice, Christina Foreman, Kyle Forouzanfar, Mohammad H. Fraser, Maya S. Fullman, Nancy Gething, Peter W. Goldberg, Ellen M. Graetz, Nicholas Haagsma, Juanita A. Hay, Simon I. Huynh, Chantal Johnson, Catherine O. Kassebaum, Nicholas J. Kinfu, Yohannes et al. (October 2016). "Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015". Lancet. 388 (10053): 1459–1544. doi:10.1016/S0140-6736(16)31012-1. PMC5388903 . PMID27733281.
  10. ^
  11. "Endometriosis: Overview". nichd.nih.gov. Archived from the original on 18 May 2017 . Retrieved 20 May 2017 .
  12. ^
  13. "Endometriosis: Condition Information". nichd.nih.gov. Archived from the original on 30 April 2017 . Retrieved 20 May 2017 .
  14. ^
  15. Koninckx, Philippe R. Meuleman, Christel Demeyere, Stephan Lesaffre, Emmanuel Cornillie, Freddy J. (April 1991). "Suggestive evidence that pelvic endometriosis is a progressive disease, whereas deeply infiltrating endometriosis is associated with pelvic pain". Fertility and Sterility. 55 (4): 759–765. doi:10.1016/s0015-0282(16)54244-7. PMID2010001.
  16. ^ ab
  17. Culley L, Law C, Hudson N, Denny E, Mitchell H, Baumgarten M, Raine-Fenning N (1 November 2013). "The social and psychological impact of endometriosis on women's lives: a critical narrative review". Human Reproduction Update. 19 (6): 625–39. doi: 10.1093/humupd/dmt027 . PMID23884896.
  18. ^ abcdefg
  19. Zondervan KT, Becker CM, Missmer SA (March 2020). "Endometriosis". N. Engl. J. Med. 382 (13): 1244–1256. doi:10.1056/NEJMra1810764. PMID32212520.
  20. ^
  21. Nnoaham, Kelechi E. Hummelshoj, Lone Webster, Premila d'Hooghe, Thomas de Cicco Nardone, Fiorenzo de Cicco Nardone, Carlo Jenkinson, Crispin Kennedy, Stephen H. Zondervan, Krina T. World Endometriosis Research Foundation Global Study of Women's Health consortium (August 2011). "Impact of endometriosis on quality of life and work productivity: a multicenter study across ten countries". Fertility and Sterility. 96 (2): 366–373.e8. doi:10.1016/j.fertnstert.2011.05.090. ISSN1556-5653. PMC3679489 . PMID21718982.
  22. ^ ab
  23. Vercellini P, Eskenazi B, Consonni D, Somigliana E, Parazzini F, Abbiati A, Fedele L (1 March 2011). "Oral contraceptives and risk of endometriosis: a systematic review and meta-analysis". Human Reproduction Update. 17 (2): 159–70. doi: 10.1093/humupd/dmq042 . PMID20833638.
  24. ^
  25. Buck Louis GM, Hediger ML, Peterson CM, Croughan M, Sundaram R, Stanford J, Chen Z, Fujimoto VY, Varner MW, Trumble A, Giudice LC (August 2011). "Incidence of endometriosis by study population and diagnostic method: the ENDO study". Fertil. Steril. 96 (2): 360–5. doi:10.1016/j.fertnstert.2011.05.087. PMC3143230 . PMID21719000.
  26. ^ abc
  27. Shafrir AL, Farland LV, Shah DK, Harris HR, Kvaskoff M, Zondervan K, Missmer SA (August 2018). "Risk for and consequences of endometriosis: A critical epidemiologic review". Best Practice & Research. Clinical Obstetrics & Gynecology. 51: 1–15. doi:10.1016/j.bpobgyn.2018.06.001. PMID30017581.
  28. ^ abc
  29. Brosens I (2012). Endometriosis: Science and Practice. John Wiley & Sons. p. 3. ISBN9781444398496 .
  30. ^ ab
  31. Stratton P, Berkley KJ (2011). "Chronic pelvic pain and endometriosis: translational evidence of the relationship and implications". Human Reproduction Update. 17 (3): 327–46. doi:10.1093/humupd/dmq050. PMC3072022 . PMID21106492.
  32. ^
  33. Colette S, Donnez J (July 2011). "Are aromatase inhibitors effective in endometriosis treatment?". Expert Opinion on Investigational Drugs. 20 (7): 917–31. doi:10.1517/13543784.2011.581226. PMID21529311. S2CID19463907.
  34. ^ abc
  35. Gałczyński, Krzysztof Jóźwik, Maciej Lewkowicz, Dorota Semczuk-Sikora, Anna Semczuk, Andrzej (2019-11-07). "Ovarian endometrioma – a possible finding in adolescent girls and young women: a mini-review". Journal of Ovarian Research. 12 (1): 104. doi:10.1186/s13048-019-0582-5. ISSN1757-2215. PMC6839067 . PMID31699129. Text was copied from this source, which is available under a Creative Commons Attribution 4.0 International License.
  36. ^ abc
  37. "What are the symptoms of endometriosis?". National Institutes of Health . Retrieved 2018-10-04 .
  38. ^
  39. Brown J, Farquhar C (March 2014). "Endometriosis: an overview of Cochrane Reviews". The Cochrane Database of Systematic Reviews (3): CD009590. doi:10.1002/14651858.cd009590.pub2. PMC6984415 . PMID24610050.
  40. ^ ab
  41. Ballard K, Lane H, Hudelist G, Banerjee S, Wright J (June 2010). "Can specific pain symptoms help in the diagnosis of endometriosis? A cohort study of women with chronic pelvic pain". Fertility and Sterility. 94 (1): 20–7. doi:10.1016/j.fertnstert.2009.01.164. PMID19342028.
  42. ^ [page needed]
  43. Murray MT, Pizzorno J (2012). The Encyclopedia of Natural Medicine (3rd ed.). New York, NY: Simon and Schuster.
  44. ^
  45. Asante A, Taylor RN (2011). "Endometriosis: the role of neuroangiogenesis". Annual Review of Physiology. 73: 163–82. doi:10.1146/annurev-physiol-012110-142158. PMID21054165.
  46. ^
  47. "Treatment of infertility in women with endometriosis". uptodate.com . Retrieved 2017-12-18 .
  48. ^
  49. Wolthuis AM, Meuleman C, Tomassetti C, D'Hooghe T, de Buck van Overstraeten A, D'Hoore A (November 2014). "Bowel endometriosis: colorectal surgeon's perspective in a multidisciplinary surgical team". World Journal of Gastroenterology. 20 (42): 15616–23. doi:10.3748/wjg.v20.i42.15616. PMC4229526 . PMID25400445.
  50. ^
  51. Arbique D, Carter S, Van Sell S (September 2008). "Endometriosis can evade diagnosis". Rn. 71 (9): 28–32, quiz 33. PMID18833741.
  52. ^
  53. Pearce CL, Templeman C, Rossing MA, Lee A, Near AM, Webb PM, Nagle CM, Doherty JA, Cushing-Haugen KL, Wicklund KG, Chang-Claude J, Hein R, Lurie G, Wilkens LR, Carney ME, Goodman MT, Moysich K, Kjaer SK, Hogdall E, Jensen A, Goode EL, Fridley BL, Larson MC, Schildkraut JM, Palmieri RT, Cramer DW, Terry KL, Vitonis AF, Titus LJ, Ziogas A, Brewster W, Anton-Culver H, Gentry-Maharaj A, Ramus SJ, Anderson AR, Brueggmann D, Fasching PA, Gayther SA, Huntsman DG, Menon U, Ness RB, Pike MC, Risch H, Wu AH, Berchuck A (April 2012). "Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies". The Lancet. Oncology. 13 (4): 385–94. doi:10.1016/S1470-2045(11)70404-1. PMC3664011 . PMID22361336.
  54. ^ Nezhat F. Article by Prof. Farr Nezhat, MD, FACOG, FACS, University of Columbia, May 1, 2012Archived November 2, 2012, at the Wayback Machine
  55. ^
  56. Audebert A (April 2005). "[Women with endometriosis: are they different from others?]" [Women with endometriosis: are they different from others?]. Gynécologie, Obstétrique & Fertilité (in French). 33 (4): 239–46. doi:10.1016/j.gyobfe.2005.03.010. PMID15894210.
  57. ^
  58. Rowlands IJ, Nagle CM, Spurdle AB, Webb PM (December 2011). "Gynecological conditions and the risk of endometrial cancer". Gynecologic Oncology. 123 (3): 537–41. doi:10.1016/j.ygyno.2011.08.022. PMID21925719.
  59. ^
  60. Rousset, P. Rousset-Jablonski, C. Alifano, M. Mansuet-Lupo, A. Buy, J.-N. Revel, M.-P. (March 2014). "Thoracic endometriosis syndrome: CT and MRI features". Clinical Radiology. 69 (3): 323–330. doi:10.1016/j.crad.2013.10.014. ISSN1365-229X. PMID24331768.
  61. ^
  62. Reis FM, Coutinho LM, Vannuccini S, Luisi S, Petraglia F (2020). "Is Stress a Cause or a Consequence of Endometriosis?". Reproductive Sciences. 27 (1): 39–45. doi:10.1007/s43032-019-00053-0. PMID32046437. S2CID209896867. CS1 maint: uses authors parameter (link)
  63. ^
  64. Acosta S, Leandersson U, Svensson SE, Johnsen J (May 2001). "[A case report. Endometriosis caused colonic ileus, ureteral obstruction and hypertension]" [A case report. Endometriosis caused colonic ileus, ureteral obstruction and hypertension]. Lakartidningen (in Swedish). 98 (18): 2208–12. PMID11402601.
  65. ^
  66. Ueda Y, Enomoto T, Miyatake T, Fujita M, Yamamoto R, Kanagawa T, Shimizu H, Kimura T (June 2010). "A retrospective analysis of ovarian endometriosis during pregnancy". Fertility and Sterility. 94 (1): 78–84. doi:10.1016/j.fertnstert.2009.02.092. PMID19356751.
  67. ^
  68. Visouli AN, Zarogoulidis K, Kougioumtzi I, Huang H, Li Q, Dryllis G, Kioumis I, Pitsiou G, Machairiotis N, Katsikogiannis N, Papaiwannou A, Lampaki S, Zaric B, Branislav P, Porpodis K, Zarogoulidis P (October 2014). "Catamenial pneumothorax". Journal of Thoracic Disease. 6 (Suppl 4): S448-60. doi:10.3978/j.issn.2072-1439.2014.08.49. PMC4203986 . PMID25337402.
  69. ^ abc
  70. McCann MR, Schenk WB, Nassar A, Maimone S (September 2020). "Thoracic endometriosis presenting as a catamenial hemothorax with discordant video-assisted thoracoscopic surgery". Radiol Case Rep. 15 (9): 1419–1422. doi:10.1016/j.radcr.2020.05.064. PMC7334551 . PMID32642009.
  71. ^
  72. Wise, Jacqui (2016-04-01). "Women with endometriosis show higher risk for heart disease". BMJ. 353: i1851. doi:10.1136/bmj.i1851. ISSN1756-1833. PMID27036948. S2CID28699291.
  73. ^
  74. "Women with endometriosis at higher risk for heart disease | American Heart Association". newsroom.heart.org . Retrieved 2018-07-03 .
  75. ^ abcdefg
  76. Fauser BC, Diedrich K, Bouchard P, Domínguez F, Matzuk M, Franks S, Hamamah S, Simón C, Devroey P, Ezcurra D, Howles CM (2011). "Contemporary genetic technologies and female reproduction". Human Reproduction Update. 17 (6): 829–47. doi:10.1093/humupd/dmr033. PMC3191938 . PMID21896560.
  77. ^ ab Kapoor D, Davila W (2005). Endometriosis, Archived 2007-11-11 at the Wayback MachineeMedicine.
  78. ^
  79. Giudice LC, Kao LC (2004). "Endometriosis". Lancet. 364 (9447): 1789–99. doi:10.1016/S0140-6736(04)17403-5. PMID15541453. S2CID208788714.
  80. ^
  81. Rahmioglu N, Nyholt DR, Morris AP, Missmer SA, Montgomery GW, Zondervan KT (September 2014). "Genetic variants underlying risk of endometriosis: insights from meta-analysis of eight genome-wide association and replication datasets". Human Reproduction Update. 20 (5): 702–16. doi:10.1093/humupd/dmu015. PMC4132588 . PMID24676469.
  82. ^
  83. "MUC16 mucin 16, cell surface associated [Homo sapiens (human)] - Gene - NCBI". ncbi.nlm.nih.gov . Retrieved 2018-11-13 .
  84. ^
  85. "FN1 fibronectin 1 [Homo sapiens (human)] - Gene - NCBI". ncbi.nlm.nih.gov . Retrieved 2018-11-13 .
  86. ^ ab
  87. Giudice LC (June 2010). "Clinical practice. Endometriosis". The New England Journal of Medicine. 362 (25): 2389–98. doi:10.1056/NEJMcp1000274. PMC3108065 . PMID20573927.
  88. ^
  89. Treloar SA, Bell TA, Nagle CM, Purdie DM, Green AC (June 2010). "Early menstrual characteristics associated with subsequent diagnosis of endometriosis". American Journal of Obstetrics and Gynecology. 202 (6): 534.e1–6. doi:10.1016/j.ajog.2009.10.857. PMID20022587.
  90. ^
  91. Nnoaham KE, Webster P, Kumbang J, Kennedy SH, Zondervan KT (September 2012). "Is early age at menarche a risk factor for endometriosis? A systematic review and meta-analysis of case-control studies". Fertility and Sterility. 98 (3): 702–712.e6. doi:10.1016/j.fertnstert.2012.05.035. PMC3502866 . PMID22728052.
  92. ^
  93. Anger DL, Foster WG (January 2008). "The link between environmental toxicant exposure and endometriosis". Frontiers in Bioscience. 13 (13): 1578–93. doi:10.2741/2782. PMID17981650.
  94. ^
  95. Guo SW (2004). "The link between exposure to dioxin and endometriosis: a critical reappraisal of primate data". Gynecologic and Obstetric Investigation. 57 (3): 157–73. doi:10.1159/000076374. PMID14739528. S2CID29701466.
  96. ^
  97. Guo SW, Simsa P, Kyama CM, Mihályi A, Fülöp V, Othman EE, D'Hooghe TM (October 2009). "Reassessing the evidence for the link between dioxin and endometriosis: from molecular biology to clinical epidemiology". Molecular Human Reproduction. 15 (10): 609–24. doi: 10.1093/molehr/gap075 . PMID19744969.
  98. ^
  99. Rier S, Foster WG (December 2002). "Environmental dioxins and endometriosis". Toxicological Sciences. 70 (2): 161–70. doi:10.1093/toxsci/70.2.161. PMID12441361.
  100. ^ abcdef
  101. van der Linden PJ (November 1996). "Theories on the pathogenesis of endometriosis". Human Reproduction. 11 Suppl 3: 53–65. doi: 10.1093/humrep/11.suppl_3.53 . PMID9147102.
  102. ^ abcd
  103. Hufnagel D, Li F, Cosar E, Krikun G, Taylor HS (September 2015). "The Role of Stem Cells in the Etiology and Pathophysiology of Endometriosis". Seminars in Reproductive Medicine. 33 (5): 333–40. doi:10.1055/s-0035-1564609. PMC4986990 . PMID26375413.
  104. ^
  105. Koninckx, PR (1999). "Implantation versus infiltration: the Sampson versus the endometriotic disease theory". Gynecol Obstet Invest. 47 (Supplement 1): 3–9. doi:10.1159/000052853. PMID10087422. S2CID29718095.
  106. ^
  107. Pinkert TC, Catlow CE, Straus R (April 1979). "Endometriosis of the urinary bladder in a man with prostatic carcinoma". Cancer. 43 (4): 1562–7. doi: 10.1002/1097-0142(197904)43:4<1562::aid-cncr2820430451>3.0.co2-w . PMID445352.
  108. ^ ab
  109. Signorile PG, Baldi F, Bussani R, D'Armiento M, De Falco M, Baldi A (April 2009). "Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer". Journal of Experimental & Clinical Cancer Research. 28: 49. doi:10.1186/1756-9966-28-49. PMC2671494 . PMID19358700.
  110. ^
  111. Mok-Lin EY, Wolfberg A, Hollinquist H, Laufer MR (February 2010). "Endometriosis in a patient with Mayer-Rokitansky-Küster-Hauser syndrome and complete uterine agenesis: evidence to support the theory of coelomic metaplasia". Journal of Pediatric and Adolescent Gynecology. 23 (1): e35-7. doi:10.1016/j.jpag.2009.02.010. PMID19589710.
  112. ^ ab
  113. Marsh EE, Laufer MR (March 2005). "Endometriosis in premenarcheal girls who do not have an associated obstructive anomaly". Fertility and Sterility. 83 (3): 758–60. doi:10.1016/j.fertnstert.2004.08.025. PMID15749511.
  114. ^
  115. Thibodeau LL, Prioleau GR, Manuelidis EE, Merino MJ, Heafner MD (April 1987). "Cerebral endometriosis. Case report". Journal of Neurosurgery. 66 (4): 609–10. doi:10.3171/jns.1987.66.4.0609. PMID3559727.
  116. ^
  117. Rodman MH, Jones CW (April 1962). "Catamenial hemoptysis due to bronchial endometriosis". The New England Journal of Medicine. 266 (16): 805–8. doi:10.1056/nejm196204192661604. PMID14493132.
  118. ^
  119. "Endopædia". endopaedia.info . Retrieved 2018-07-03 .
  120. ^
  121. Gleicher N, el-Roeiy A, Confino E, Friberg J (July 1987). "Is endometriosis an autoimmune disease?". Obstetrics and Gynecology. 70 (1): 115–22. PMID3110710.
  122. ^
  123. Capellino S, Montagna P, Villaggio B, Sulli A, Soldano S, Ferrero S, Remorgida V, Cutolo M (June 2006). "Role of estrogens in inflammatory response: expression of estrogen receptors in peritoneal fluid macrophages from endometriosis". Annals of the New York Academy of Sciences. 1069 (1): 263–7. Bibcode:2006NYASA1069..263C. doi:10.1196/annals.1351.024. PMID16855153. S2CID35601442.
  124. ^ ab
  125. Young VJ, Brown JK, Saunders PT, Horne AW (2013). "The role of the peritoneum in the pathogenesis of endometriosis". Human Reproduction Update. 19 (5): 558–69. doi: 10.1093/humupd/dmt024 . PMID23720497.
  126. ^
  127. Redwine DB (October 2002). "Was Sampson wrong?". Fertility and Sterility. 78 (4): 686–93. doi:10.1016/S0015-0282(02)03329-0. PMID12372441.
  128. ^
  129. Sampson JA (March 1927). "Metastatic or Embolic Endometriosis, due to the Menstrual Dissemination of Endometrial Tissue into the Venous Circulation". Am. J. Pathol. 3 (2): 93–110.43. PMC1931779 . PMID19969738.
  130. ^ ab
  131. Sampson, JA (1927). "Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity". Am J Obstet Gynecol. 14 (4): 422–469. doi:10.1016/S0002-9378(15)30003-X.
  132. ^
  133. Bruner-Tran KL, Yeaman GR, Crispens MA, Igarashi TM, Osteen KG (May 2008). "Dioxin may promote inflammation-related development of endometriosis". Fertility and Sterility. 89 (5 Suppl): 1287–98. doi:10.1016/j.fertnstert.2008.02.102. PMC2430157 . PMID18394613.
  134. ^
  135. Yuk JS, Shin JS, Shin JY, Oh E, Kim H, Park WI (2015). "Nickel Allergy Is a Risk Factor for Endometriosis: An 11-Year Population-Based Nested Case-Control Study". PLOS ONE. 10 (10): e0139388. Bibcode:2015PLoSO..1039388Y. doi:10.1371/journal.pone.0139388. PMC4594920 . PMID26439741.
  136. ^ ab
  137. Wellbery, Caroline (1999-10-15). "Diagnosis and Treatment of Endometriosis". American Family Physician. American Academy of Family Physicians. 60 (6): 1753–62, 1767–8. PMID10537390. Archived from the original on 2011-06-06 . Retrieved 2011-07-26 .
  138. ^
  139. Laschke MW, Giebels C, Menger MD (2011). "Vasculogenesis: a new piece of the endometriosis puzzle". Human Reproduction Update. 17 (5): 628–36. doi: 10.1093/humupd/dmr023 . PMID21586449.
  140. ^
  141. Morotti M, Vincent K, Brawn J, Zondervan KT, Becker CM (2014). "Peripheral changes in endometriosis-associated pain". Human Reproduction Update. 20 (5): 717–36. doi:10.1093/humupd/dmu021. PMC4337970 . PMID24859987.
  142. ^
  143. Yuk JS, Park EJ, Seo YS, Kim HJ, Kwon SY, Park WI (March 2016). "Graves Disease Is Associated With Endometriosis: A 3-Year Population-Based Cross-Sectional Study". Medicine. 95 (10): e2975. doi:10.1097/MD.0000000000002975. PMC4998884 . PMID26962803.
  144. ^
  145. Giudice LC, Kao LC (2004). "Endometriosis". Lancet. 364 (9447): 1789–99. doi:10.1016/S0140-6736(04)17403-5. PMID15541453. S2CID208788714.
  146. ^ abcdef
  147. Scutiero G, Iannone P, Bernardi G, Bonaccorsi G, Spadaro S, Volta CA, Greco P, Nappi L (2017). "Oxidative Stress and Endometriosis: A Systematic Review of the Literature". Oxidative Medicine and Cellular Longevity. 2017: 7265238. doi:10.1155/2017/7265238. PMC5625949 . PMID29057034.
  148. ^ abcd
  149. Uzunçakmak C, Güldaş A, Ozçam H, Dinç K (2013). "Scar endometriosis: a case report of this uncommon entity and review of the literature". Case Reports in Obstetrics and Gynecology. 2013: 386783. doi:10.1155/2013/386783. PMC3665185 . PMID23762683.
  150. ^
  151. Weed JC, Ray JE (May 1987). "Endometriosis of the bowel". Obstetrics and Gynecology. 69 (5): 727–30. PMID3574800.
  152. ^
  153. Dwivedi AJ, Agrawal SN, Silva YJ (February 2002). "Abdominal wall endometriomas". Digestive Diseases and Sciences. 47 (2): 456–61. doi:10.1023/a:1013711314870. PMID11855568. S2CID7362461.
  154. ^
  155. Kaunitz A, Di Sant'Agnese PA (December 1979). "Needle tract endometriosis: an unusual complication of amniocentesis". Obstetrics and Gynecology. 54 (6): 753–5. PMID160025.
  156. ^
  157. Koger KE, Shatney CH, Hodge K, McClenathan JH (September 1993). "Surgical scar endometrioma". Surgery, Gynecology & Obstetrics. 177 (3): 243–6. PMID8356497.
  158. ^
  159. Andres MP, Arcoverde FV, Souza CC, Fernandes LF, Abrao MS, Kho RM (February 2020). "Extrapelvic Endometriosis: A Systematic Review". J Minim Invasive Gynecol. 27 (2): 373–389. doi:10.1016/j.jmig.2019.10.004. PMID31618674.
  160. ^ abcdef
  161. Johnson NP, Hummelshoj L (June 2013). "Consensus on current management of endometriosis". Human Reproduction. 28 (6): 1552–68. doi: 10.1093/humrep/det050 . PMID23528916.
  162. ^
  163. Nisenblat, V Prentice, L Bossuyt, PM Farquhar, C Hull, ML Johnson, N (13 July 2016). "Combination of the non-invasive tests for the diagnosis of endometriosis". The Cochrane Database of Systematic Reviews. 7: CD012281. doi:10.1002/14651858.CD012281. PMC6458001 . PMID27405583.
  164. ^
  165. "Getting diagnosed with endometriosis | Endometriosis UK". endometriosis-uk.org . Retrieved 2018-06-13 .
  166. ^ abcde
  167. Nisenblat V, Bossuyt PM, Farquhar C, Johnson N, Hull ML (February 2016). "Imaging modalities for the non-invasive diagnosis of endometriosis". The Cochrane Database of Systematic Reviews. 2: CD009591. doi:10.1002/14651858.cd009591.pub2. PMC7100540 . PMID26919512.
  168. ^
  169. Chapron C, Marcellin L, Borghese B, Santulli P (November 2019). "Rethinking mechanisms, diagnosis and management of endometriosis". Nat Rev Endocrinol. 15 (11): 666–682. doi:10.1038/s41574-019-0245-z. PMID31488888. S2CID201838966.
  170. ^
  171. "Reclassifying endometriosis as a syndrome would benefit patient care - The BMJ" . Retrieved 17 August 2020 .
  172. ^ abc
  173. Hsu AL, Khachikyan I, Stratton P (June 2010). "Invasive and noninvasive methods for the diagnosis of endometriosis". Clin Obstet Gynecol. 53 (2): 413–9. doi:10.1097/GRF.0b013e3181db7ce8. PMC2880548 . PMID20436318.
  174. ^
  175. Nisolle M, Paindaveine B, Bourdon A, Berlière M, Casanas-Roux F, Donnez J (June 1990). "Histologic study of peritoneal endometriosis in infertile women". Fertility and Sterility. 53 (6): 984–8. doi:10.1016/s0015-0282(16)53571-7. PMID2351237.
  176. ^
  177. Practice Committee of the American Society for Reproductive Medicine (April 2014). "Treatment of pelvic pain associated with endometriosis: a committee opinion". Fertility and Sterility. 101 (4): 927–35. doi:10.1016/j.fertnstert.2014.02.012. PMID24630080.
  178. ^
  179. "How do health care providers diagnose endometriosis?". nichd.nih.gov/ . Retrieved 2019-05-06 .
  180. ^ abcdefg
  181. "Endometriosis – Diagnosis, treatment and patient experiences". Swedish Agency for Health Technology Assessment and Assessment of Social Services (SBU). 2018-05-04 . Retrieved 2018-06-13 .
  182. ^ ab
  183. Fang J, Piessens S (June 2018). "A step‐by‐step guide to sonographic evaluation of deep infiltrating endometriosis". Sonography. 5 (2): 67–75. doi: 10.1002/sono.12149 .
  184. ^ abc
  185. Wild M, Pandhi S, Rendle J, Swift I, Ofuasia E (October 2020). "MRI for the diagnosis and staging of deeply infiltrating endometriosis: a national survey of BSGE accredited endometriosis centres and review of the literature". Br J Radiol. 93 (1114): 20200690. doi:10.1259/bjr.20200690. PMC 7548358. PMID32706984.
  186. ^
  187. American Society For Reproductive (May 1997). "Revised American Society for Reproductive Medicine classification of endometriosis: 1996". Fertility and Sterility. 67 (5): 817–21. doi:10.1016/S0015-0282(97)81391-X. PMID9130884.
  188. ^
  189. Vercellini P, Fedele L, Aimi G, Pietropaolo G, Consonni D, Crosignani PG (January 2007). "Association between endometriosis stage, lesion type, patient characteristics and severity of pelvic pain symptoms: a multivariate analysis of over 1000 patients". Human Reproduction. 22 (1): 266–71. doi: 10.1093/humrep/del339 . PMID16936305.
  190. ^ abcde
  191. May KE, Conduit-Hulbert SA, Villar J, Kirtley S, Kennedy SH, Becker CM (2010). "Peripheral biomarkers of endometriosis: a systematic review". Human Reproduction Update. 16 (6): 651–74. doi:10.1093/humupd/dmq009. PMC2953938 . PMID20462942.
  192. ^ ab
  193. Hirsch M, Duffy J, Davis CJ, Nieves Plana M, Khan KS (October 2016). "Diagnostic accuracy of cancer antigen 125 for endometriosis: a systematic review and meta-analysis". BJOG. 123 (11): 1761–8. doi:10.1111/1471-0528.14055. PMID27173590. S2CID22744182.
  194. ^
  195. May KE, Villar J, Kirtley S, Kennedy SH, Becker CM (2011). "Endometrial alterations in endometriosis: a systematic review of putative biomarkers". Human Reproduction Update. 17 (5): 637–53. doi: 10.1093/humupd/dmr013 . PMID21672902.
  196. ^
  197. Gupta, D Hull, ML Fraser, I Miller, L Bossuyt, PM Johnson, N Nisenblat, V (20 April 2016). "Endometrial biomarkers for the non-invasive diagnosis of endometriosis". The Cochrane Database of Systematic Reviews. 4: CD012165. doi:10.1002/14651858.CD012165. PMC6953323 . PMID27094925.
  198. ^
  199. Taghavipour M, Sadoughi F, Mirzaei H, Yousefi B, Moazzami B, Chaichian S, Mansournia MA, Asemi Z (2020). "Apoptotic functions of microRNAs in pathogenesis, diagnosis, and treatment of endometriosis". Cell and Bioscience. 10: 12. doi:10.1186/s13578-020-0381-0. PMC7014775 . PMID32082539.
  200. ^
  201. Aurelia Busca, Carlos Parra-Herran. "Ovary - nontumor - Nonneoplastic cysts / other - Endometriosis". Pathology Outlines. Topic Completed: 1 August 2017. Revised: 5 March 2020
  202. ^
  203. "Archived copy" (PDF) . Archived (PDF) from the original on 2013-05-02 . Retrieved 2013-07-18 . CS1 maint: archived copy as title (link)
  204. ^
  205. Bourdel N, Alves J, Pickering G, Ramilo I, Roman H, Canis M (2014). "Systematic review of endometriosis pain assessment: how to choose a scale?". Human Reproduction Update. 21 (1): 136–52. doi: 10.1093/humupd/dmu046 . PMID25180023.
  206. ^ ab
  207. "What are the treatments for endometriosis". Eunice Kennedy Shriver National Institute of Child Health and Human Development. Archived from the original on 3 August 2013 . Retrieved 20 August 2013 .
  208. ^
  209. Moen MH, Rees M, Brincat M, Erel T, Gambacciani M, Lambrinoudaki I, Schenck-Gustafsson K, Tremollieres F, Vujovic S, Rozenberg S (September 2010). "EMAS position statement: Managing the menopause in women with a past history of endometriosis". Maturitas. 67 (1): 94–7. doi:10.1016/j.maturitas.2010.04.018. PMID20627430.
  210. ^ abcdef
  211. Wellbery C (October 1999). "Diagnosis and treatment of endometriosis". American Family Physician. 60 (6): 1753–62, 1767–8. PMID10537390. Archived from the original on 2013-10-29.
  212. ^
  213. "What are the treatments for endometriosis?". National Institute of Child Health and Human Development. January 31, 2017 . Retrieved November 20, 2019 .
  214. ^ abc
  215. Vercellini, Paolo Viganò, Paola Somigliana, Edgardo Fedele, Luigi (May 2014). "Endometriosis: pathogenesis and treatment". Nature Reviews. Endocrinology. Springer Science and Business Media LLC. 10 (5): 261–275. doi:10.1038/nrendo.2013.255. ISSN1759-5029. PMID24366116. S2CID13050344. CS1 maint: date and year (link)
  216. ^
  217. Speroff L, Glass RH, Kase NG (1999). Clinical Gynecologic Endocrinology and Infertility (6th ed.). Lippincott Willimas Wilkins. p. 1057. ISBN0-683-30379-1 .
  218. ^
  219. "Endometriosis and Infertility: Can Surgery Help?" (PDF) . American Society for Reproductive Medicine. 2008. Archived (PDF) from the original on 2010-10-11 . Retrieved 31 Oct 2010 .
  220. ^
  221. Dunselman, G. A. J. Vermeulen, N. Becker, C. Calhaz-Jorge, C. D'Hooghe, T. De Bie, B. Heikinheimo, O. Horne, A. W. Kiesel, L. Nap, A. Prentice, A. Saridogan, E. Soriano, D. Nelen, W. (2014-01-15). "ESHRE guideline: management of women with endometriosis". Human Reproduction (Oxford, England). Oxford University Press (OUP). 29 (3): 400–412. doi: 10.1093/humrep/det457 . ISSN0268-1161. PMID24435778.
  222. ^ ab
  223. Liakakos T, Thomakos N, Fine PM, Dervenis C, Young RL (2001). "Peritoneal adhesions: etiology, pathophysiology, and clinical significance. Recent advances in prevention and management". Digestive Surgery. 18 (4): 260–73. doi:10.1159/000050149. PMID11528133. S2CID30816909.
  224. ^
  225. Trehan AK (2002). "Temporary ovarian suspension". Gynaecological Endoscopy. 11 (1): 309–314. doi:10.1046/j.1365-2508.2002.00520.x.
  226. ^
  227. Abuzeid MI, Ashraf M, Shamma FN (February 2002). "Temporary ovarian suspension at laparoscopy for prevention of adhesions". The Journal of the American Association of Gynecologic Laparoscopists. 9 (1): 98–102. doi:10.1016/S1074-3804(05)60114-4. PMID11821616.
  228. ^
  229. Zorbas KA, Economopoulos KP, Vlahos NF (July 2015). "Continuous versus cyclic oral contraceptives for the treatment of endometriosis: a systematic review". Archives of Gynecology and Obstetrics. 292 (1): 37–43. doi:10.1007/s00404-015-3641-1. PMID25644508. S2CID23340983.
  230. ^
  231. Patel B, Elguero S, Thakore S, Dahoud W, Bedaiwy M, Mesiano S (2014). "Role of nuclear progesterone receptor isoforms in uterine pathophysiology". Human Reproduction Update. 21 (2): 155–73. doi:10.1093/humupd/dmu056. PMC4366574 . PMID25406186.
  232. ^https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/017557s033s039s040s041s042lbl.pdf
  233. ^ ab
  234. Brown J, Pan A, Hart RJ (December 2010). "Gonadotrophin-releasing hormone analogues for pain associated with endometriosis". The Cochrane Database of Systematic Reviews (12): CD008475. doi:10.1002/14651858.CD008475.pub2. PMC7388859 . PMID21154398.
  235. ^
  236. Attar E, Bulun SE (May 2006). "Aromatase inhibitors: the next generation of therapeutics for endometriosis?". Fertility and Sterility. 85 (5): 1307–18. doi:10.1016/j.fertnstert.2005.09.064. PMID16647373.
  237. ^
  238. Nawathe A, Patwardhan S, Yates D, Harrison GR, Khan KS (June 2008). "Systematic review of the effects of aromatase inhibitors on pain associated with endometriosis". BJOG. 115 (7): 818–22. doi:10.1111/j.1471-0528.2008.01740.x. PMID18485158. S2CID205614747.
  239. ^
  240. "What Are NSAIDs for Arthritis". WebMD.com. 14 December 2018 . Retrieved 2 September 2020 .
  241. ^
  242. "NSAIDs: Therapeutic use and variability of response in adults". UpToDate.com. 17 January 2020 . Retrieved 2 September 2020 .
  243. ^
  244. Flower A, Liu JP, Lewith G, Little P, Li Q (May 2012). "Chinese herbal medicine for endometriosis". The Cochrane Database of Systematic Reviews (5): CD006568. doi:10.1002/14651858.CD006568.pub3. PMID22592712.
  245. ^
  246. Lu D, Song H, Li Y, Clarke J, Shi G (January 2012). "Pentoxifylline for endometriosis". The Cochrane Database of Systematic Reviews. 1: CD007677. doi:10.1002/14651858.CD007677.pub3. PMID22258970.
  247. ^
  248. "Practice bulletin no. 114: management of endometriosis". Obstetrics and Gynecology. 116 (1): 223–36. July 2010. doi:10.1097/AOG.0b013e3181e8b073. PMID20567196.
  249. ^ ab
  250. Laschke MW, Menger MD (2012). "Anti-angiogenic treatment strategies for the therapy of endometriosis". Human Reproduction Update. 18 (6): 682–702. doi: 10.1093/humupd/dms026 . PMID22718320.
  251. ^
  252. Canny GO, Lessey BA (May 2013). "The role of lipoxin A4 in endometrial biology and endometriosis". Mucosal Immunology. 6 (3): 439–50. doi:10.1038/mi.2013.9. PMC4062302 . PMID23485944.
  253. ^
  254. Streuli I, de Ziegler D, Santulli P, Marcellin L, Borghese B, Batteux F, Chapron C (February 2013). "An update on the pharmacological management of endometriosis". Expert Opinion on Pharmacotherapy. 14 (3): 291–305. doi:10.1517/14656566.2013.767334. PMID23356536. S2CID10052884.
  255. ^
  256. Valiani M, Ghasemi N, Bahadoran P, Heshmat R (2010). "The effects of massage therapy on dysmenorrhea caused by endometriosis". Iranian Journal of Nursing and Midwifery Research. 15 (4): 167–71. PMC3093183 . PMID21589790.
  257. ^ abcd
  258. "Endometrios – diagnostik, behandling och bemötande". sbu.se (in Swedish). Statens beredning för medicinsk och social utvärdering (SBU) Swedish Agency for Health Technology Assessment and Assessment of Social Services. 2018-05-04. p. 121 . Retrieved 2018-06-13 .
  259. ^
  260. Kaiser A, Kopf A, Gericke C, Bartley J, Mechsner S (September 2009). "The influence of peritoneal endometriotic lesions on the generation of endometriosis-related pain and pain reduction after surgical excision". Archives of Gynecology and Obstetrics. 280 (3): 369–73. doi:10.1007/s00404-008-0921-z. PMID19148660. S2CID21133672.
  261. ^
  262. Radosa MP, Bernardi TS, Georgiev I, Diebolder H, Camara O, Runnebaum IB (June 2010). "Coagulation versus excision of primary superficial endometriosis: a 2-year follow-up". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 150 (2): 195–8. doi:10.1016/j.ejogrb.2010.02.022. PMID20303642.
  263. ^ ab [non-primary source needed]
  264. Wurn BF, Wurn LJ, Patterson K, King CR, Scharf ES (2011). "Decreasing dyspareunia and dysmenorrhea in women with endometriosis via a manual physical therapy: Results from two independent studies". Journal of Endometriosis and Pelvic Pain Disorders. 3 (4): 188–196. doi:10.5301/JE.2012.9088. PMC6154826 . Archived from the original on 2013-10-29.
  265. ^
  266. Chen I, Veth VB, Choudhry AJ, Murji A, Zakhari A, Black AY, Agarpao C, Maas JW (18 November 2020). "Pre- and postsurgical medical therapy for endometriosis surgery". Cochrane Database Syst Rev. 11: CD003678. doi:10.1002/14651858.CD003678.pub3. PMID33206374.
  267. ^
  268. Bulletti, Carlo Coccia, Maria Battistoni, Sylvia Borini, Andrea (August 2010). "Endometriosis and infertility". Journal of Assisted Reproduction and Genetics. 27 (8): 441–447. doi:10.1007/s10815-010-9436-1. PMC2941592 . PMID20574791.
  269. ^
  270. Selçuk İ, Bozdağ G (2013). "Recurrence of endometriosis risk factors, mechanisms and biomarkers review of the literature". J Turk Ger Gynecol Assoc. 14 (2): 98–103. doi:10.5152/jtgga.2013.52385. PMC3881735 . PMID24592083.
  271. ^
  272. Guo SW (2009). "Recurrence of endometriosis and its control". Human Reproduction Update. 15 (4): 441–61. doi: 10.1093/humupd/dmp007 . PMID19279046.
  273. ^
  274. Nothnick WB (June 2011). "The emerging use of aromatase inhibitors for endometriosis treatment". Reproductive Biology and Endocrinology. 9: 87. doi:10.1186/1477-7827-9-87. PMC3135533 . PMID21693036.
  275. ^
  276. Bulun SE, Zeitoun K, Sasano H, Simpson ER (1999). "Aromatase in aging women". Seminars in Reproductive Endocrinology. 17 (4): 349–58. doi:10.1055/s-2007-1016244. PMID10851574.
  277. ^
  278. Batt RE, Mitwally MF (December 2003). "Endometriosis from thelarche to midteens: pathogenesis and prognosis, prevention and pedagogy". Journal of Pediatric and Adolescent Gynecology. 16 (6): 337–47. doi:10.1016/j.jpag.2003.09.008. PMID14642954.
  279. ^ ab
  280. Guo, S.-W. (2009-03-11). "Recurrence of endometriosis and its control". Human Reproduction Update. 15 (4): 441–461. doi: 10.1093/humupd/dmp007 . ISSN1355-4786. PMID19279046.
  281. ^
  282. Batt, Ronald E. (2011). A history of endometriosis. London: Springer. pp. 13–38. doi:10.1007/978-0-85729-585-9. ISBN978-0-85729-585-9 .
  283. ^ abcdefghij
  284. Nezhat C, Nezhat F, Nezhat C (December 2012). "Endometriosis: ancient disease, ancient treatments". Fertility and Sterility. 98 (6 Suppl): S1-62. doi:10.1016/j.fertnstert.2012.08.001. PMID23084567.
  285. ^
  286. Meigs JV (November 1941). "Endometriosis—Its Significance". Ann. Surg. 114 (5): 866–74. doi:10.1097/00000658-194111000-00007. PMC1385984 . PMID17857917.
  287. ^
  288. Barbieri RL (January 1992). "Hormonal therapy of endometriosis". Infertility and Reproductive Medicine Clinics of North America. 3 (1): 187–200. The hormonal therapy of endometriosis continues to evolve. In the 1940s and 1950s, high-dose testosterone and diethylstilbestrol regimens were the only hormonal agents available in the treatment of endometriosis. These agents, although efficacious, were associated with intolerable side effects. The current armamentarium of hormonal agents-the GnRH analogues, danazol, and the synthetic progestins-is efficacious and has fewer side effects.
  289. ^ abc
  290. J. Aiman (6 December 2012). Infertility: Diagnosis and Management. Springer Science & Business Media. pp. 261–. ISBN978-1-4613-8265-2 .
  291. ^ abcd
  292. J.B. Josimovich (11 November 2013). Gynecologic Endocrinology. Springer Science & Business Media. pp. 387–. ISBN978-1-4613-2157-6 .
  293. ^ abcd
  294. Robert William Kistner (1995). Kistner's Gynecology: Principles and Practice. Mosby. p. 263. ISBN978-0-8151-7479-0 .
  295. ^
  296. Barra F, Grandi G, Tantari M, Scala C, Facchinetti F, Ferrero S (April 2019). "A comprehensive review of hormonal and biological therapies for endometriosis: latest developments". Expert Opin Biol Ther. 19 (4): 343–360. doi:10.1080/14712598.2019.1581761. PMID30763525. S2CID73455399.
  297. ^
  298. Iasimone, Ashley (January 7, 2017). "Halsey undergoes surgery to treat endometriosis". Billboard . Retrieved November 27, 2018 .
  299. ^
  300. Hayden, Jade (11 May 2020). " ' Nearly broke me' Spice Girls' Emma Bunton describes struggling to conceive with endometriosis". Her.ie . Retrieved May 28, 2021 .
  301. ^
  302. "Blossom Ball 2009 – Whoopi Goldberg". Endometriosis Foundation of America. November 27, 2007 . Retrieved January 21, 2021 .
  303. ^
  304. "Radio presenter Mel Greig's shocking photo shows reality of living with endometriosis". News.com.au. March 28, 2018 . Retrieved January 21, 2021 .
  305. ^
  306. Murray, Rheana (September 9, 2017). "Julianne Hough opens up about endometriosis: 'I just thought it was normal ' ". Today . Retrieved January 21, 2021 .
  307. ^
  308. Hustwaite, Bridget (August 14, 2018). "Endometriosis: The pain sucks, but so does just getting a diagnosis". Hack on Triple J . Retrieved January 21, 2021 .
  309. ^
  310. "Padma Lakshmi shares her struggle with endometriosis". Redbook Magazine. October 17, 2011. Archived from the original on 2 November 2020 . Retrieved March 9, 2021 – via YouTube.
  311. ^
  312. "Yellow Wiggle Emma Watkins opens up about the agony of endometriosis". PerthNow. March 16, 2019 . Retrieved January 21, 2021 .
  313. ^ ab
  314. Gao X, Outley J, Botteman M, Spalding J, Simon JA, Pashos CL (December 2006). "Economic burden of endometriosis". Fertility and Sterility. 86 (6): 1561–72. doi:10.1016/j.fertnstert.2006.06.015. PMID17056043. S2CID20623034.
  315. ^
  316. Koltermann KC, Dornquast C, Ebert AD, Reinhold T (2017). "Economic Burden of Endometriosis: A Systematic Review". Ann Reprod Med Treat. 2 (2m): 1015. S2CID32839234.
  317. ^
  318. As-Sanie, Sawsan (August 2019). "Assessing research gaps and unmet needs in endometriosis". American Journal of Obstetrics and Gynecology. 221 (2): 86–94. doi:10.1016/j.ajog.2019.02.033. PMID30790565.
  319. ^
  320. Hudelist, G (December 2012). "Diagnostic delay for endometriosis in Austria and Germany: causes and possible consequences". Human Reproduction. 27 (12): 3412–3416. doi: 10.1093/humrep/des316 . PMID22990516.
  321. ^
  322. "Test d'auto-évaluation du JOGC". Journal of Obstetrics and Gynaecology Canada. 25 (12): 1046–1051. December 2003. doi:10.1016/s1701-2163(16)30350-4. ISSN1701-2163.
  323. ^
  324. Quibel, A (20 April 2012). "General practitioners and the challenge of endometriosis screening and care: Results of a survey". Gynécologie, obstétrique & fertilité. 41 (6): 372–380. doi:10.1016/j.gyobfe.2012.02.024. PMID22521982.
  325. ^ ab
  326. Arruda, M.S. (1 April 2003). "Time elapsed from onset of symptoms to diagnosis of endometriosis in a cohort study of Brazilian women". Human Reproduction. 18 (4): 756–759. doi: 10.1093/humrep/deg136 . PMID12660267.
  327. ^
  328. Shade, George (24 June 2011). "Endometriosis in the African American woman—racially, a different entity?". Gynecological Surgery. 9: 59–62. doi: 10.1007/s10397-011-0685-5 . S2CID6288739.
  329. ^ ab
  330. Hoffman, Kelly M. Trawalter, Sophie Axt, Jordan R. Oliver, M. Norman (2016-04-19). "Racial bias in pain assessment and treatment recommendations, and false beliefs about biological differences between blacks and whites". Proceedings of the National Academy of Sciences of the United States of America. 113 (16): 4296–4301. Bibcode:2016PNAS..113.4296H. doi:10.1073/pnas.1516047113. ISSN1091-6490. PMC4843483 . PMID27044069.
  331. ^ ab
  332. "How Being a Black Woman Impacts My Endometriosis". Healthline. 2019-06-26 . Retrieved 2021-02-20 .
  333. ^ ab
  334. Matías-González, Yatzmeli Sánchez-Galarza, Astrid N. Flores-Caldera, Idhaliz Rivera-Segarra, Eliut (2020-09-23). " " Es que tú eres una changa": stigma experiences among Latina women living with endometriosis". Journal of Psychosomatic Obstetrics and Gynaecology. 42 (1): 67–74. doi:10.1080/0167482X.2020.1822807. ISSN1743-8942. PMID32964770. S2CID221862356.

This article incorporates text in the public domain as a Swedish government "utterance" by URL§9


RESULTS

Lack of correlation between TDAG8 expression and psychosine-triggered cytokinetic defects

Psychosine is a lyso form of galactosylceramide. The biosynthetic pathway to formation of lyso-GSL is not known. Psychosine expression is observed in β-galactosylceramidase–deficient animals. Because psychosine elicits various cellular responses (Igisu and Suzuki, 1984 Hannun and Bell, 1987 Okajima and Kondo, 1995 Lloyd-Evans et al., 2003b), the mechanism of how cells respond to psychosine has been debated. It was previously suggested that the G protein–coupled receptor TDAG8 is a receptor for psychosine because TDAG8-expressing cells acquire psychosine sensitivity to induce multiploidy in RH7777 and HEK293 cells (Im et al., 2001). Subsequently TDAG8 was also proposed as a proton-sensing receptor (Wang et al., 2004). Furthermore, it was shown that macrophages from Tdag8-null mice undergo multiploidization upon psychosine treatment (Radu et al., 2006). The receptor responsible for psychosine-mediated polyploidization has yet to be identified. We compared psychosine-mediated polyploidization in U937, Namalwa, and KMS12-PE cell lines to examine the basis for induced cellular ploidy (Figure 1A). Among these cells, Namalwa B lymphoma cells were the most sensitive according to detection of 8/16N cells with 2.5 μM psychosine treatment. U937 cells were less sensitive than Namalwa cells, and myeloma KMS12-PE cells were not polyploidized with 5 μM psychosine. To determine whether TDAG8 expression correlates with psychosine-mediated multiploid cell nucleation, we examined its expression level in these cell lines (Figure 1B). TDAG8 was detected in U937 cells, whereas Namalwa and KMS12-PE cells were negative for staining. The finding that TDAG8-negative Namalwa cells had the highest sensitivity to psychosine is consistent with results in Tdag8-null macrophages, in which Radu et al. (2006) showed that TDAG8 does not seem to be involved in psychosine-induced multiploidy. Thus it is unlikely that TDAG8 functions as a specific receptor of psychosine to cause cytokinetic defects.

FIGURE 1: Cross-cell profiling of psychosine-mediated polyploidization and cellular factors. (A) Polyploidization of psychosine-treated cells. U937, Namalwa, and KMS12-PE cells were treated with 2.5 or 5 μM psychosine for 2 d before harvesting and measuring cellular DNA content by propidium iodide staining. Degree of multiploidy was expressed as average nuclear content value, where 2N represents normal diploid cells. (B) Expression of TDAG8. The same set of cell lines was assessed for TDAG8 expression. Cells were stained with anti-TDAG8 antibody and evaluated using FCM. (C) Positive correlation between the cross-cell profiles for GM1 level and psychosine-mediated polyploidization. Top, relative psychosine-mediated polyploidization profile among a set of six cell lines plotted in web-graph format. Relative PPIN values are expressed on the diagonal lines of a hexagon, with the plots located at the edge of the hexagon indicating stronger polyploidization. Cells with the strongest value were set to 100%. Middle, relative GM1 expression profile obtained by FCM staining using CTxB plotted in web-graph format. Owing to the use of fluorescence signals, data are plotted on a log scale. Bottom, Pearson’s r between these profiles and associated p value.

Quantitative determination and profiling of psychosine-mediated multiploidy

Psychosine susceptibility and resulting ploidy varied among cell types (Figure 1A). Therefore psychosine-induced multiploidy was quantified using six different B cell lines because quantitative profiling and correlation analyses of cellular phenotypes can be useful in uncovering genetic traits (Yamamoto et al., 2007). Lacking a standard procedure to quantitatively evaluate polyploidizing activity among different cell lines, we measured the nuclear status of the cell lines upon treatment with a graded dose of psychosine. Dose responses of each cell line were different for multiploidization. Therefore, to accurately quantify psychosine-mediated multiploidy, we determined the percentage of >4N cells with incremental doses of psychosine. For normalization, this value was divided by the concentration of psychosine used for each condition. The maximal value was used for each cell line to quantitatively express sensitivity for psychosine-mediated polyploidization. This value was called the psychosine-mediated ploidy index number (PPIN). When the six–cell line profile of PPIN was expressed as a web graph (Figure 1C), a similarity was found in the pattern with that of cell surface GM1 expression level, measured with the cholera toxin B subunit (CTxB), as in a previous study with the same set of cell lines (Takematsu et al., 2011). Pearson’s r between these profiles was positive (0.82). The presence of such a strong positive correlation suggested that the cell surface GM1 level can affect psychosine-mediated multiploid cell formation.

Requirement of glycosphingolipids in efficient psychosine-triggered multiploidization

The GM1 level was hypothesized to be a cellular factor determining psychosine sensitivity. GSL expression has a propensity to be cell type and state specific (Kannagi et al., 1983 Hakomori and Zhang, 1997 Sonnino et al., 2007). To evaluate this positive correlation functionally, we chose Namalwa cells for the remainder of the study because they are sensitive to polyploidization. To examine the functional participation of cellular GSLs (the biosynthetic pathway is summarized in Figure 2A) in psychosine-triggered multiploidization, we examined the effect of GM1 knockdown by means of short hairpin RNA (shRNA)–treated Namalwa cells. Two shRNA species for GM1 synthase (GM1Syn encoded by B3GALT4) exhibited a knockdown effect on CTxB staining, which probes cell surface GM1 expressed on Namalwa cells with high sensitivity (Takematsu et al., 2011). The shRNA corresponds to nucleotide residues 252–272 (Sh252-272) and 311–331 (Sh311-331), which exhibited roughly 70 and 30% reduction in flow cytometric CTxB staining relative to the control (ShLaminB), respectively (Figure 2B). The knockdown also resulted in loss of GM2 in liquid chromatography (LC)–mass spectrometry (MS) detection, whereas the Sia α2-3 Gal β1-4 Glc β1-1 Cer (GM3) level was not affected (Supplemental Figure S1). More prominent suppression in multiploidization was found in Sh252-272, as peak ploidy shifted to 4N in these cells. Although peak ploidy was 8N, similar to control, a relative increase in 2N/4N peaks was found in Sh311-331 (Figure 2C). These data indicate that cell surface GM1 levels can quantitatively modulate psychosine-triggered multiploidy.

FIGURE 2: Reduced polyploidization of Namalwa cells with decreased GM1. (A) Biosynthetic pathway of sphingolipids in Namalwa cells. Lipids are indicated in white letters on black, and enzymes are indicated by boxed black letters. Inhibitors used in this study are depicted in black letters. (B) CTxB staining of GM1Syn-knockdown Namalwa cells. Namalwa cells were infected with lentivirus encoding shRNA for control (lamin) and GM1Syn (B3GALT4) and stained with CTxB. Gray indicates control staining. Bottom, mean fluorescence intensity (MFI) values of the CTxB staining. (C) GM1Syn-knockdown cells were treated with psychosine, and ploidy of the cells was analyzed as in Figure 1A. (D) Namalwa cells were treated with various doses of PDMP overnight. Cell surface GM1 level was examined using CTxB as in Figure 2B. (E) Namalwa cells were treated with a graded dose of PDMP and 5 μM psychosine (Psy) for 2 d, and ploidy of the cells was analyzed as in Figure 1A.

To examine whether psychosine-triggered multiploidy can be artificially manipulated by chemical inhibitors, we treated cells with ( d -threo)-1-phenyl-2decanoylamino-3- morpholino-1-propanol (PDMP), a glucosylceramide synthase (GlcCerSyn) inhibitor that reduces cellular GSLs (Figure 2A Inokuchi et al., 1989). The dosage of PDMP was carefully determined because its toxicity can cause cell cycle arrest. Addition of PDMP up to 20 μM did not attenuate proliferation of Namalwa cells (Supplemental Figure S2). PDMP treatment dose dependently reduced cell surface GM1 expression in Namalwa cells (Figure 2D). In the absence of PDMP, psychosine treatment resulted in the induction of 8N and 16N peaks. These multiploid peaks were suppressed with graded doses of PDMP (Figure 2E). These data show that levels of cell surface GM1, which is reduced by knockdown of GM1Syn or PDMP treatment, can affect psychosine-mediated polyploidization.

Evaluation of the involvement of GSL species in polyploidy

Cellular GSLs are present in multiple molecular species, and their balance varies among cells. Moreover, cellular metabolism of various classes of lipids is interconnected. Thus, in general, caution should be taken in evaluating experimental results from inhibitor treatment because these chemicals can simultaneously alter other, unexpected cellular metabolic pathway(s). To circumvent these potential pitfalls, we also examined cells with GSLs altered via modulation of glycosyltransferase gene expression. The major GSL species in Namalwa cells were previously shown to be in the ganglio series (Takematsu et al., 2011). Human B cells show drastic alteration in GSL species activated germinal center B cells remodel major GSL species from the ganglio series (such as GM3, GM1) to the globo series (such as Gal α1-4 Gal β1-4 Glc β1-1 Cer [Gb3]). This was found to be due to the genetic dominance of Gb3 synthase (Gb3Syn, lactosylceramide α1-4 galactosyltransferase, encoded by A4GALT) at a pathway branch (Keusch et al., 2000 Kojima et al., 2000 Takematsu et al., 2011 Figure 3A). This dominant effect of Gb3Syn was exploited to modulate GSL expression. Of importance, Gb3Syn is a dual-function glycosyltransferase in addition to α1-4 galactosyltransferase activity, Gb3Syn can form an intra-Golgi complex with Gal β1-4 Glc β1-1 Cer (LacCer) synthase (encoded by B4GALT6). Consequently mutant Gb3Syn (Gb3Syn-TxT, in which the DxD motif of the enzyme was converted to TxT) reduced LacCer and ganglio-series GSLs in a dominant-negative manner without biosynthesizing the globo series (Figure 3B, Supplemental Figure S3, and Supplemental Table S1 Takematsu et al., 2011). Therefore Gb3Syn-TxT cells were useful for evaluating the functional importance of overall GSL expression in psychosine-triggered polyploidy without using chemical inhibitors. Consistent with PDMP-mediated GSL inhibition (Figure 2E), Gb3Syn-TxT cells (exhibiting global GSL reduction downstream of LacCer) were also less susceptible to psychosine-mediated polyploidization, showing a prominent decrease in both 8N and 16N peaks and a consequent increase in the 2N peak in the presence of psychosine (Figure 3C). Unlike PDMP treatment, Gb3Syn-TxT cells did not alter the GlcCer level (Figure 3B and Supplemental Figure S3 Takematsu et al., 2011), and yet similar suppression of psychosine-mediated polyploidization was found in these cells (Figure 3C). This result was consistent with the suggestion that reduced GM1 can negatively modulate psychosine-triggered multiploidization. To examine the level effects of different glycolipid species, we introduced Gb3Syn into Namalwa cells, in which the major GSL species was shifted to Gb3 (Figure 3B Takematsu et al., 2011). Unlike Gb3Syn-TxT cells, Gb3Syn cells exhibited comparable multiploidization upon psychosine addition. This result indicates that psychosine-mediated multiploidization is not altered by the change from ganglio- to globo-series GSL(s) (Figure 3C). These results suggest that specific GSL species such as GM1 and Gb3 can have similar effects in enhancing psychosine-triggered multiploidization.

FIGURE 3: Effects of molecular GSL species. (A) Flowchart of GSL biosynthetic pathway branching in Namalwa cells. Gb3Syn dominantly regulates the biosynthetic pathway, and thus can effectively alter GSL profiles in Namalwa cells. (B) TLC analysis of sphingolipid species in vector, Gb3Syn, and Gb3Syn-TxT cells. Namalwa cells transfected with MSCV-IRES-EGFP virus (vector), MSCV-Gb3Syn-IRES-EGFP virus (Gb3Syn), and MSCV-Gb3Syn-TxT-IRES-EGFP virus (Gb3Syn-TxT) were polyclonally sorted by GFP positivity. Sphingolipids purified from these cells were analyzed by TLC. Lipids were separated in chloroform, methanol, and water (65:25:4). SM was visualized with primulin, and GSLs were visualized with orcinol-sulfate. The mobility of standard lipids is indicated. Relative mean band densities are plotted from three experimental replicates (bottom). Doublet bands on TLC were calculated separately when possible. (C) Effect of expression of Gb3Syn-TxT and Gb3Syn on psychosine-induced polyploidization. These cells were treated with psychosine, and polyploidization was measured as in Figure 1A.

Enhanced psychosine-induced multiploidization upon introduction of GlcCerSyn

Reductions of GSL resulted in resistance to psychosine-triggered multiploidization (Figures 2D and 3C). Induction of GSL was used to examine enhanced cellular response to psychosine. GlcCerSyn (encoded by UGCG) responsible for cellular GSL levels was expressed to induce GSL levels. When GlcCerSyn was introduced into Namalwa cells, the ploidy value was not different from control cells. However, psychosine induced ploidy of the cells (Figure 4A). Because the difference in polyploidy was less than twofold, this experiment was repeated five times to confirm the reproducibility and statistical significance (Figure 4B). These data indicate that levels of GSLs quantitatively affect psychosine-triggered multiploidization.

FIGURE 4: Enhancement of psychosine-induced polyploidization by cellular GSL. (A) Enhanced polyploidization of Namalwa cells infected with GlcCerSyn. Namalwa cells were transfected with MSCV-IRES-EGFP virus (GFP) and MSCV-GlcCerSyn-IRES-EGFP virus (GlcCerSyn) and polyclonally sorted by GFP positivity. Psychosine-triggered polyploidization was measured by FCM as in Figure 1A. (B) Quantification of GlcCerSyn-enhanced nuclear ploidy triggered by psychosine. The quantified mean nuclear ploidy from five independent experiments with graded psychosine (Psy) dose is plotted with SEM. Statistical significance was assessed using Student’s t test as indicated above the bars (*p < 0.05). (C) TLC analyses of cells transfected with GlcCerSyn and nSMase2. Namalwa cells used in Figure 3A were transfected with retrovirus MSCV-IRES-Blast virus (Blast) and MSCV-nSMase2-IRES-Blast virus (nSMase2) to produce four different types of cells. Sphingolipids were extracted from these cells and analyzed by TLC as in Figure 3B. (D) Additive effect of GlcCerSyn and nSMase2 expression on psychosine-triggered polyploidization. Psychosine-induced multiploidy was analyzed as in Figure 1A.

Additive effect of GlcCerSyn and sphingomyelinase

Modulation of GlcCerSyn expression reduces ceramide, as well as increases GSLs (Figure 2A and Supplemental Figure S3). Was the increase in GSLs or reduction in ceramide responsible for this phenotypic change? In addition to the de novo pathway, ceramide is also produced by sphingomyelinase (SMase). SM is strongly expressed on the plasma membrane and thus could serve as a source of ceramide. Among SMases, neutral SMase2 (nSMase2) functions to scramble ceramide from SM on the cell surface thus, nSMase2 is a good candidate to alter the SM/ceramide balance (Hofmann et al., 2000 Marchesini et al., 2003 Tani and Hannun, 2007). Unlike GlcCerSyn expression, nSMase2 expression was expected to increase ceramide levels, although both of these enzymes favor the biosynthesis of GSLs downstream. When nSMase2 was expressed, ∼10% suppression in SM was detected by densitometry in TLC analyses (Figure 4C). By contrast, expression levels of Glc β1-1 Cer (GlcCer), LacCer, and GM3 were not affected. To account for the loss of SM, ceramide was increased threefold in nSMase2 cells in the lipidomic LC-MS analysis (Supplemental Figure S3). GlcCerSyn expression caused more apparent changes in GSL levels: approximate twofold increase in GlcCer and LacCer and ∼25% increase in GM3 on TLC and LC-MS (Figure 4C and Supplemental Figure S3). In both cases, we detected sensitization of Namalwa cells to psychosine-induced polyploidization (Figure 4D). These data indicate that an increase in GSLs rather than a reduction in ceramide sensitizes Namalwa cells to psychosine-mediated inhibition of cytokinesis to produce multiploid cells. The effects of GlcCerSyn and nSMase2 were additive because simultaneous expression of both enzymes resulted in the most sensitive phenotype to psychosine (Figure 4D). Of note, 2N cells were barely detectable under this condition, indicating that nearly the entire population of cells in culture was prevented from achieving cytokinesis by psychosine.

Specificity of lysosphingolipid species on multiploidy

It was previously reported that both psychosine and glucopsychosine (GlcPsy) can induce U937 multiploidization (Kanazawa et al., 2000). Because the combination of Gb3Syn-TxT Namalwa cells and GlcCerSyn/nSMase2 Namalwa cells was a useful system for analyzing the effect of membrane GSLs, we used it to examine the effect of other lysosphingolipid species on multiploidization. Consistently, as with U937 cells, GlcPsy induced Namalwa cell multiploidization, whereas lyso-LacCer and sphingosylphosphorylcholine (SPC) did not (Supplemental Figure S4A). Similar to psychosine treatment (Figure 3C), Gb3Syn-TxT cells (reduced GSLs) were less polyploidized by GlcPsy. Unlike psychosine treatment (Figure 4D), GlcCerSyn/nSMase2 expression did not enhance GlcPsy-mediated polyploidization at a concentration of 5 μM (Supplemental Figure S4B) compared with control cells. In this condition, however, 2N cells were almost undetectable even in the controls. We titrated GlcPsy concentration to examine GlcCerSyn/nSMase2-mediated enhancement in GlcPsy-triggered multiploidization. At 1.25 μM, GlcPsy more efficiently induced GlcCerSyn/nSMase2 cell multiploidy than with controls (Supplemental Figure S4C). This enhancement was not increased at 2.5 μM GlcPsy probably due to the very efficient multiploidization-stimulating activity of GlcPsy.

Cell type–specific effect of GlcCerSyn expression

Given that membrane GSL can modulate psychosine susceptibility, GlcCerSyn elevation was examined to alter the psychosine sensitivity of unresponsive cells. Myeloma KMS12-PE cells were resistant to psychosine-induced multiploidy (Figure 1A). Introduction of GlcCerSyn in KMS12-PE cells did not alter this resistance (Supplemental Figure S5). Thus psychosine sensitivity can be modulated by GSL expression levels in susceptible cells (such as Namalwa cells), but cellular GSL levels alone do not sensitize cells to psychosine instead, there may be a bona fide receptor affected by GSL levels.

Suppression of psychosine susceptibility by sphingomyelin

Because nSMase2 cells exhibited enhanced psychosine-triggered polyploidization, we evaluated SM as a cellular factor controlling psychosine susceptibility (Figure 4D). SM was presumed to be independent of cellular GSLs because single nSMase2 introduction did not alter the GSL level (Figure 4C). We pretreated Namalwa cells with incremental doses of SM. Unlike GSL treatment of Namalwa cells, which had no effect (Supplemental Figure S6), SM treatment attenuated psychosine-mediated multiploidization in dose-dependent way (Figure 5A). When cell surface SM was digested by bacterial SMase (bSMase) treatment, which reduced SM levels and increased GSL levels (Supplemental Figure S7), enhanced psychosine-triggered multiploidy was detected (Figure 5A). Therefore SM levels can negatively modulate the psychosine effect. To perturb cellular GSL/SM biosynthesis with enzyme gene expression, we introduced SM synthase (SMS) cDNAs into Namalwa cells. SMS occurs in two isoforms: Golgi-specific SMS1 (Yamaoka et al., 2004) and plasma membrane/Golgi–specific SMS2 (Tafesse et al., 2007). In Namalwa cells, SMS1 was strongly expressed and SMS2 expression was weak, according to Western blotting of FLAG-tagged SMS proteins (Figure 5B). The apparent presence of the SM cycling pathway (Hannun, 1994) kept the cells from increasing SM levels >∼20% in SMS2 cells by TLC (Figure 5C). Lipidomic LC-MS showed a more prominent (∼30%) induction of SM in both SMS1 and SMS2 cells (Supplemental Figure S3). Therefore we used these cells for functional analyses of SM levels for psychosine-triggered multiploidization.

FIGURE 5: Suppressed psychosine-induced polyploidization by induction of SM. (A) Effect of SM and bacterial SMase (bSMase) treatment on psychosine-induced polyploidization. Namalwa cells were treated with 10 or 20 μM SM or 50 mU/ml bSMase with 5 μM psychosine (Psy). Cellular DNA content was determined as in Figure 1A. (B) Expression of SMS1/2 as detected by Western blotting. Namalwa cells were transfected with pSP72-EF1-IRES-Blast vector (vector) and pSP72-EF1-SMS1/2-IRES-Blast vector (SMS1/2) stable transfectants were selected as polyclonal mixtures. Whole-cell lysates were prepared, and transgene-derived SMS1/2 was detected using anti-FLAG M2 antibody. (C) Effect of SMS1/2 on cellular levels of sphingolipids. Sphingolipids were isolated from these cells and analyzed by TLC as in Figure 3B. (D) Detection of cell surface SM by NT-lysenin. Induction of cell surface SM upon SMS introduction was detected using the GST-NT-lysenin probe by FCM. SM-bound lysenin was visualized as a complex with anti-GST and FITC-conjugated anti-goat IgG. Gray indicates control staining, and solid dashed black lines indicate Namalwa cells transfected with control vectors. (E) Effect of SMS1/2 expression on psychosine-induced polyploidization. SMS-transfected Namalwa cells were examined for psychosine-induced polyploidization as in Figure 1A. (F) Quantification of psychosine-mediated polyploidization in SMS-overexpressing cells. Psychosine-induced polyploidization was determined, and mean ploidy values of six independent experiments are expressed as percentage decrease from vector control. Statistical significance of the difference between SMS1 compared with vector is p < 0.05 and SMS2 compared with vector is p < 0.1.

Cell surface SM level and organization were monitored using NT-lysenin, an earthworm toxin specifically targeting SM clusters. Monomeric recombinant NT-lysenin was shown to be useful for SM detection (Ishitsuka and Kobayashi, 2004). When SMS1 and SMS2 cells were stained with NT-lysenin, consistent with the data from TLC analyses, a detectable increase in cell surface SM was observed (Figure 5D). Comparison of these cells with vector-transformed control cells showed suppressed psychosine-mediated polyploidization in both SMS1 and SMS2 cells (Figure 5E). Because the effect was subtle, the mean ploidy was calculated from six independent experiments, and results are expressed as the difference from control (Figure 5F). These data indicate that increased SM expression relative to GSL/GM1 can be a modulatory factor in psychosine sensitivity. A stronger effect in SMS1 cells than in SMS2 cells can be interpreted as a difference in the intracellular localization of these two isoforms. Collectively these results indicate that increased SM:GSL ratio reduces susceptibility to psychosine. When other parameters are fixed, SM expression negatively and GSL expression positively modulate psychosine-triggered multiploidization of Namalwa cells.

Suppressed cell surface SM clustering and phosphatidylinositol 4,5-bisphosphate production by psychosine

SM can be present on the cell membrane as clusters or domains. Here the phrase “cluster of lipids” is used to indicate small aggregates composed of <10 lipid molecules (Ishitsuka et al., 2004). By contrast, a “domain” is the specific area of the membrane with high labeling density of lipid-binding proteins. Here we examined the effect of psychosine on SM clusters. HeLa cells undergoing cytokinesis showed lysenin-positive SM cluster enrichment in the outer membrane of cleavage furrows (Abe et al., 2012). Subcellular localization of SM was examined in relation to the cleavage furrow using a monomeric NT-lysenin probe, which avoids formation of probe-mediated SM aggregation (Ishitsuka and Kobayashi, 2004). Psychosine treatment reduced NT-lysenin staining by flow cytometry in Namalwa cells (Figure 6A). Equinatoxin II is another SM-binding probe that preferentially binds to SM even when dispersed (Makino et al., 2015). In sharp contrast to lysenin, equinatoxin II stained both control and psychosine-treated cells with roughly equal intensity (Figure 6A), indicating that the abundance in cell surface SM per se was not attenuated. Thus psychosine attenuated SM clustering, which was presumably caused by cholesterol-mediated partitioning of the membrane. When psychosine-treated cells were examined under a fluorescence microscope, consistent overall reduction in lysenin staining was detected in both dividing (Figure 6B) and nondividing cells. Taken together, the data show that psychosine disrupts outer leaflet SM clustering, where phosphatidylinositol-4-phosphate 5-kinase is recruited to biosynthesize phosphatidylinositol 4,5-bisphosphate (PIP2) at the inner leaflet of the membrane (Abe et al., 2012). For further evaluation, we detected PIP2 production in the cleavage furrows of dividing cells using the PH–green fluorescent protein (GFP) probe, which contains the PH domain from PLCδ (Field et al., 2005). The cleavage furrow PIP2 level is important for furrow ingression at anaphase (Field et al., 2005). Therefore we examined psychosine-mediated loss of the cleavage furrow PH-GFP signal in cells during late mitosis. Cleavage furrows of psychosine-treated cells showed a reduced PH-GFP signal more prominently in anaphasic cells (Figure 6, C and D), indicating that psychosine disrupted SM clustering, which is associated with accumulation of PIP2 at the cleavage furrow. The number of telophasic cells (with enlongated cleavage furrow) was reduced upon psychosine treatment, probably caused by the defect in anaphase of psychosine-treated cells. Such results were consistent and more prominent in GlcPsy cells, whereas nonpolyploidizing lyso-LacCer and SPC did not exhibit any of these effects, despite similar physical properties shared by all of these lysosphingolipids (Figure 6, C and D). Therefore we propose that specific disruption of SM clusters by psychosine at the anaphase cleavage furrow causes compromised PIP2 production, which results in failed cytokinesis at a later stage.

FIGURE 6: Alteration of cell surface SM expression upon psychosine treatment. (A) Cell surface expression of SM upon psychosine treatment. Namalwa cells were treated with 5 μM psychosine (Psy) overnight and stained with recombinant GST-NT-lysenin, which detects cluster SM as in Figure 5D, or with NT-equinatoxin II-GFP-His, for total SM. (B) Cell surface localization of the NT-lysenin signal upon psychosine treatment. Namalwa cells were treated with 5 μM psychosine overnight and stained with recombinant EGFP-NT-lysenin. EGFP fluorescence was detected using fluorescence microscopy. Four independent cells in late mitotic phases (two anaphasic and two telophasic) are shown for each condition. To represent the varied distribution found in the psychosine-treated samples, each of the four typical staining patterns is displayed. (C) Attenuated PIP2-binding PH-GFP probe signals in psychosine-treated Namalwa cells. Namalwa cells expressing PH-GFP (PLCδ1-PH-GFP) were treated with 5 μM each lysosphingolipid overnight, and the GFP signal was observed in mitotic cells. (D) Calculation of ratio of cells observed in Figure 6C. We counted 120 cells in late mitotic phases. Incidence of anaphasic and telophasic cells was determined from cell body shapes and DAPI signal. Both anaphasic and telophasic cells were assessed for enrichment of PH-GFP signal in the cleavage furrow.


NCERT Solutions For Class 11 Biology Cell Cycle and Cell Division

Topics and Subtopics in NCERT Solutions for Class 11 Biology Chapter 10 Cell Cycle and Cell Division:

Section Name Topic Name
10 Cell Cycle and Cell Division
10.1 Cell Cycle
10.2 M Phase
10.3 Significance of Mitosis
10.4 Meiosis
10.5 Significance of Meiosis
10.6 Summary

NCRT TEXTBOOK QUESTIONS SOLVED

1. What is the average cell cycle span for a mammalian cell?
Solution: 24 hours.

2. Distinguish cytokinesis from karyokinesis.
Solution: Differences between cytokinesis and karyokinesis are:

More Resources for CBSE Class 11

3. Describe the events taking place during the interphase.
Solution: The interphase, though called the resting phase, is metabolically quite active. It is the time during which the cell prepares itself for division by undergoing both cell growth and DNA replication in an orderly manner. The interphase is further divided into three phases:
• G1 (Gap 1) phase
• S (Synthesis) phase
• G2 (Gap 2) phase
G1 phase corresponds to the interval between mitosis of previous cell cycle and initiation of DNA replication. During G1 phase the cell is metabolically active and grows continuously but does not replicate its DNA S or synthesis phase marks the period during which DNA synthesis or replication takes place. During this time the amount of DNA doubles per cell. In animal cells, during the S phase, DNA replication occurs in the nucleus, and the centriole duplicates in the cytoplasm. During the G2 phase synthesis of DNA stops while cell growth continues with synthesis of protein and RNA in preparation for mitosis.

4. What is G0 (quiescent phase) of cell cycle?
Solution: G0 phase is the phase of inactivation of cell cycle due to non-availability of mitogens and energy rich compounds. Cells in this stage remain metabolically active but no longer proliferate i.e., do not grow or differentiate unless called on to do so depending on the requirement of the organism. E.g., Nerve and heart cells of chordates are in permanent G0 phase.

5. Why is mitosis called equational division?
Solution: Mitosis is a type of cell division in which chromosomes replicate and become equally distributed in two daughter nuclei so that the daughter cells come to have the same number and type of chromosomes as present in parent cell. So mitosis is called as equational division.

6. Name the stage of cell cycle at which each one of the following events occur:
(i) Chromosomes are moved to spindle equator.
(ii) Centromere splits and chromatids separate.
(iii) Pairing between homologous chromosomes takes place.
(iv) Crossing over between homologous chromosomes takes place.
Solution:
(i) Metaphase
(ii) Anaphase
(iii) Zygotene of prophase I of meiosis 1
(iv) Pachytene of prophase I of meiosis I

7. Describe the following:
(a) Synapsis
(b) Bivalent
(c) Chiasmata
Draw a diagram to illustrate your answer.
Solution:
(a) Synapsis: During zygotene of prophase I stage homologou s chromosomes start pairing together and this process of association is called synapsis. Electron micrographs of this stage indicate that chromosome synapsis is accompanied by the formation of complex structure called synaptonemal complex.
(b) Bivalent: The complex formed by a pair of synapsed homologous chromosomes is called a bivalent or a tetrad i.e., 4 chromatids or a pair of chromosomes.

(c) Chiasmata: The beginning of diplotene is recognized by the dissolution of the synaptonemal complex and the tendency of the synapsed homologous chromosomes of the bivalents to separate from each other except at the sites of crossovers. These points of attachment (X-shaped structures) between the homologous chromosomes are called chiasmata.

8. How does cytokinesis in plant cells differ from that in animal cells?
Solution: Plant cytokinesis and animal cytokinesis differ in following respects:

9. Find examples where the four daughter cells from meiosis are equal in size and where they are found unequal in size.
Solution: During formation of male gametes (i.e., spermatozoa) in a typical mammal (i.e., human being), the four daughter cells formed from meiosis are equal in size. On the other hand, during formation of female gamete (i.e., ovum) in a typical mammal (i.e., human being), the four daughter cells are unequal in size.

10. Can there be DNA replication without cell division?
Solution: Yes. Endomitosis is the multiplication of chromosomes present in a set in nucleus without karyokinesis and cytokinesis result-ing in numerous copies within each cell. It is of 2 types.
Polyteny: Here chromosomes divide and redivide without separation of chromatids so that such chromosomes become multistranded with many copies of DNA. Such polytene (many stranded) chromosomes remain in permanent prophase stage and do not undergo cell cycle e.g., polytene (salivary glands) chromosome of Drosophila has 512- 1024 chromatids. Here number of sets of chromosomes does not change.
Polyploidy (endoduplication) : Here all chromosomes in a set divide and its chromatids separate but nucleus does not divide. This results in an increase in number of sets of chromosomes in the nucleus (4x, 8x….). This increase in sets of chromosomes is called polyploidy. It can be induced by colchicine and granosan. These chromosomes are normal and undergo cell cycle.

11. List the main differences between mitosis and meiosis.
Solution:

12. Distinguish anaphase of mitosis from anaphase I of meiosis.
Solution: Anaphase of mitosis : It is the phase of shortest duration. APC (anaphase promoting complex) develops. It degenerates proteins -binding the two chromatids in the region of centromere. As a result, the centromere of each chromosome divides. This converts the two chromatids into daughter chromosomes each being attached to the spindle pole of its side by independent chromosomal fibre. The chromosomes move towards the spindle poles with the centromeres projecting towards the poles and the limbs trailing behind. There is corresponding shortening of chromosome fibres. The two pole-ward moving chromosomes of each type remain attached to each other by interzonal fibres. Ultimately, two groups of chromosomes come to lie at the spindle poles.

Anaphase I of meiosis : Chiasmata disappear completely and the homologous chromosomes separate. The process is called disjunction. The separated chromosomes (univalents) show divergent chromatids and are called dyads. They move towards the spindle poles and ultimately form two groups of haploid chromosomes.

13. What is the significance of meiosis?
Solution: The significance of meiosis is given below:
(i) Formation of gametes – Meiosis forms gametes that are essential for sexual reproduction.
(ii) Genetic information – It switches on the genetic information for the development of gametes or gametophytes and switches off the sporophytic information. ‘
(iii) Maintenance of chromosome number – Meiosis maintains the fixed number of chromosomes in sexually reproducing organisms by halving the same. It is essential since the chromosome number becomes double after fertilisation.
(iv) Assortment of chromosomes – In meiosis paternal and maternal chromosomes assort independently. It causes reshuffling of chromosomes and the traits controlled by them. The variations help the breeders in improving the races of useful plants and animals.
(v) Crossing over – It introduces new combination of traits or variations.
(vi) Mutations – Chromosomal and genomic mutations can take place by irregularities of meiotic divisions. Some of these mutations are useful to the organism and are perpetuated by natural selection.
(vii) Evidence of basic relationship of organisms – Details of meiosis are essentially similar in the majority of organisms showing their basic similarity and relationship.

14. Discuss with your teacher about
(i) haploid insects and lower plants where cell division occurs, and
(ii)some haploid cells in higher plants where cell division does not occur.
Solution:
(i) Cell division occurs in haploid insect, such as drones of honey bee and lower plant like gametophyte of algae, bryophytes, and pteridophytes.
(ii) Synergids and antipodals in embryo sac of ovule are haploid cells where cell division does not occur.

15. Can there be mitosis without DNA replication in S-phase?
Solution: No there cannot be any mitotic division without-DNA replication in ‘S’ phase.


Paola Vigano

Paola Vigano’s background is in cell biology with emphasis to the reproductive system cell biology. She obtained her biological degree at the University of Milan in 1989 and a post-graduate residency in Experimental Endocrinology at the School of Pharmacy of the same University in 2000. She obtained her PhD in Prenatal Medicine at the University of Siena in 2003.

Dr Vigano has published over 200 peer-reviewed papers and review articles and has about 6000 citations. Her research activity has been particularly devoted to cellular mechanisms underlying endometrial pathophysiology with a scientific production in the field of endometriosis basic research that has been consistent for over 25 years, in strict collaboration with most of the leading experts in the field. She is presently recognised as the 4th world leader in endometriosis by Experscape ranking, Palo Alto.

For her scientific activity, she has received a journal prize from Fertility & Sterility and two awards from the Society for Gynecologic Investigation for co-authored contributions.

From 2006 to 2009 she was the deputy coordinator of the ESHRE Special Interest Group in Endometrium and Endometriosis, from 2011 to 2014 an associated editor of Human Reproduction Update, and is presently an associated editor of Human Reproduction. She is currently President of the Italian Society of Human Reproduction (SIRU). She is member of the Endometriosis Treatment Italian Club, of the Center for Research in Obstetrics and Gynecology, Milan, and has been one of the founding member of AENDO (Associazione Italiana Dolore Pelvico ed Endometriosi).

Dr Vigano was appointed to the WES board of directors in May 2017.

� - 2021 World Endometriosis Society | Page Last Updated: 19 May 2021


Watch the video: Mitosis vs. Meiosis: Side by Side Comparison (January 2023).