Molecular Biology of Endometriosis

Sengupta, Jayasree; Anupa, G.; Bhat, Muzaffer Ahmed; Ghosh, Debabrata

doi:10.1002/9781118849613.ch3

Cited by 8 publications

(14 citation statements)

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“…Amongst several theories on the pathogenesis of endometriosis, Sampson’s theory postulating that viable endometrial cells deposited at ectopic sites due to retrograde menstruation implant, grow and eventually result in the histogenesis of endometriosis has received wide acceptance [1]. Although retrograde menstruation and exfoliated endometrial cells in the peritoneal cavity are reportedly present in most cycling women, approximately 10% of women in the reproductive age group suffer from endometriosis [1, 2]. It is therefore conjectured that there are other factors possibly at play in the endometrium that predispose a subgroup of women towards the histogenesis of endometriosis at ectopic sites.…”

Section: Introductionmentioning

confidence: 99%

Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility

Bhat

Sharma

Roy

et al. 2019

Reprod Biol Endocrinol

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Background Previous studies, which were primarily based on the fluorescent in-situ hybridisation (FISH) technique, revealed conflicting evidence regarding male foetal microchimerism in endometriosis. FISH is a relatively less sensitive technique, as it is performed on a small portion of the sample. Additionally, the probes used in the previous studies specifically detected centromeric and telomeric regions of Y chromosome, which are gene-sparse heterochromatised regions. In the present study, a panel of molecular biology tools such as qPCR, expression microarray, RNA-seq and qRT-PCR were employed to examine the Y chromosome microchimerism in the endometrium using secretory phase samples from fertile and infertile patients with severe (stage IV) ovarian endometriosis (OE) and without endometriosis. Methods Microarray expression analysis followed by validation using RNA-seq and qRT-PCR experiments at the RNA levels and further validation at the DNA level by qPCR of target inserts for selected targets in eutopic endometrium samples obtained from control (CON) and stage IV ovarian endometriosis (OE), either from fertile (FCON and FOE; n = 30/each) or infertile (ICON and IOE; n = 30/each) women, were performed. Results Six coding (AMELY, PCDH11, SRY, TGIF2LY, TSPY3, and USP9Y) and 10 non-coding (TTTY2, TTTY4C, TTTY5, TTTYY6, TTTY8, TTTY10, TTTY14, TTTY21, TTTY22, and TTTY23) genes exhibited a bimodal pattern of expression characterised by low expression in samples from fertile patients and high expression in samples from infertile patients. Seven coding MSY-linked genes (BAGE, CD24, EIF1AY, NLGN4Y, PRKY, VCY and ZFY) exhibited differential regulation in microarray analysis, and this change was validated by RNA-seq or qRT-PCR. DNA inserts for 7 genes in various samples were validated by qPCR. The prevalence and concentration of PCR-positive target inserts for BAGE, PRKY, TTTY9A and ZFY displayed higher values in the fertile, control (FCON) patients compared with the fertile, endometriosis patients (FOE). Conclusion Several coding and non-coding MSY-linked genes displayed microchimerism as evidenced by the presence of their respective DNA inserts, along with their differential transcript expression, in the endometrium during endometriosis and in cases of infertility. Electronic supplementary material The online version of this article (10.1186/s12958-019-0465-z) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility

Bhat

Sharma

Roy

et al. 2019

Reprod Biol Endocrinol

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“…Typically, a biomarker is a characteristic that may be any substance, structure, or process in the body or its products and can be objectively measured and evaluated as an indicator of biological processes, normal or pathogenic, or pharmacologic responses to a therapeutic Adapted from Espada et al 7 and Taylor et al 10 Table 2: Potential peripheral biomarkers for endometriosis. [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] Target material Name of the molecule(s) Markers may be specific to type and stage of the disease, and more correlated to specific symptom(s) of the disease (e.g., pain, infertility). None of these markers are fool-proof.…”

Section: Diagnostic Optionsmentioning

confidence: 99%

Examining Diagnostic Options and Classification Systems Available for Endometriosis

Ghosh

Sengupta

2021

EMJ Repro Health

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Introduction: Endometriosis is characterised by the presence of endometrium-like tissue outside the uterus, and is often associated with chronic pelvic pain, infertility, and compromised quality of life. Development of reliable methods of early diagnosis, staging, and classification of endometriosis would allow for restriction of disease progression by its early detection and strategising towards its early treatment and management. Diagnostic options: Typically, diagnosis and staging of endometriosis include a history and physical examination followed by clinical, imaging, and laparoscopic findings. Surgical inspection of lesions at laparoscopy with histological confirmation remains the most reliable procedure towards the detection of endometriosis and its classification. Although there are many putative peripheral biomarkers having potential diagnostic values for endometriosis, further studies are necessary for their validation. Classification systems: Based on anatomical, clinical, imaging, and several pathophysiological findings, various classifications and staging systems of endometriosis, e.g., revised American Society for Reproductive Medicine (rASRM), ENZIAN, Endometriosis Fertility Index (EFI) and Foci–Ovarian endometrioma–Adhesion–Tubal endometriosis–Inflammation (FOATI) scoring systems, have so far been postulated. However, there is no fool-proof diagnostic and classification approach available for the disease due to the general failure of current systems to reflect reproducible correlation with the major symptoms of endometriosis. Conclusion: A ‘toolbox approach’, using all the available diagnostic and classification systems maximising the information available to healthcare providers and females, is a recent recommendation. Development of collaborative research networks for the harmonisation of patient information, biological sample collection, and its storage, and that of methodological and analytical tools in a wider patient base is necessary to discover reliable leads for future diagnostic options and a classification system for endometriosis.

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“…For example, rectovaginal endometriotic nodules generally show glandular epithelium deeply embedded in the fibromuscular tissue with scanty stroma [4,5], while OE may present with little endometrial epithelium [6]. Several cellular pathophysiological processes like enhanced cell survivability and proliferation, anomalous immune-inflammatory responses, epithelialmesenchymal transition (EMT), higher invasive and adhesive capacity, reduction in apoptosis, and enhanced Ovarian Cancer; ERBB: Erb-B2 Receptor tyrosine kinase 2; ESR1: Estrogen Receptor 1; ET: Ectopic Tissue; FBXW7: F-Box and WD repeat domain containing 7; FGFR2: Fibroblast Growth Factor Receptor 2; FMT: Fibroblast-to-Myofibroblast Trans-differentiation; FOXA1: Forkhead box A1; FOXO1: Forkhead box O1; GATA3: GATA binding protein 3; GOF: Gain of Function; HMG1: High Mobility Group box 1; HRAS: Harvey Rat Sarcoma viral oncogene homolog; IGFBP1: Insulin like Growth Factor Binding Protein 1; KRAS: KRAS proto-oncogene; GTPase; Let-7: Lethal (let- angiogenesis appear to be integral to the histogenesis of endometriosis [7]. However, the etiopathologic factors that underlie the origins and progressions of this complex disease remain as yet elusive and contentious giving rise to several theories regarding etiopathology of endometriosis.…”

Section: Introductionmentioning

confidence: 99%

“…Based on histopathological and molecular characteristics, predisposing factors and antecedent processes, Varma and colleagues [45] have identified marked similarities between malignancy and endometriosis. The cellular processes which are considered to be crucial during the multistep development of human tumors, for example, unmitigated proliferative signaling, repression of growth suppressors, higher cell viability, inducement of angiogenesis, and activated invasion and migration are seen in endometriosis [7]. However, fundamental characteristics of cancer, such as genomic instability and the alteration of DNA repair genes are not found in endometriosis [46].…”

Section: Introductionmentioning

confidence: 99%

“…Long back, Scott [47] however raised some serious doubts whether endometriosis is indeed a benign disorder. Based on several lines of evidence, it appears plausible that, endometrial cells refluxed into the pelvic peritoneal niche undergo adhesion, survival and growth resulting in ET lesion due to innate physiological defects, and in the process of disease progression, oncogenic transformation occurs in the vulnerable cells in the high risk population [7,28,30,[48][49][50]. In the present narrative review paper, we make an integrated attempt to undertake evidencebased examination of the link between endometriosis and cancer at different levels.…”

Section: Introductionmentioning

confidence: 99%

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How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

Ghosh

Anupa

et al. 2019

COGO

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Endometriosis is an inflammatory disease characterized by the presence of endometrium-like tissue outside the uterus primarily on pelvic organs and tissues. It affects up to 15% of women in the reproductive age group and is often associated with pelvic pain and subfertility. Different theories explain how retrograde menstruation gives rise to endometrial deposits at ectopic sites, and how several other factors are involved in the progression of the disease. Its final diagnosis is established through direct visualization at laparoscopy or surgery followed by histological confirmation. Available epidemiological reports along with histopathological observations and molecular studies shed interesting light on the pathogenetic basis of different variants of the disease like deep infiltrating endometriosis and ovarian endometriosis. Evidence also suggests that endometriosis is a neoplastic condition which serves as a precursor of ovarian and endometrial cancers. In the present review, we have attempted to take a stock of the current epidemiological and molecular knowledge regarding endometriosis associated cancers and develop a model of functional network with interactions among critical genomic factors regulating cellular processes leading to fibrotic reaction. It is being conjectured that cyclic bleeding associated with inflammatory and oxidative stress followed by repeated tissue injury and repair along with recurrent estrogenic stimulation and ovulatory events in the pelvic environment bring about the complex phenotype of atypical endometriosis and associated neoplasm with a trade-off malignant transformation in high risk population. Finally, we have presented an algorithm for pre-emptive monitoring and management of endometriosis-associated cancers.

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Molecular Biology of Endometriosis

Cited by 8 publications

References 272 publications

Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility

Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility

Examining Diagnostic Options and Classification Systems Available for Endometriosis

How Benign is Endometriosis: Multi-Scale Interrogation of Documented Evidence

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