H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

Colón-Caraballo, Mariano; Monteiro, Janice; Flores, Idhaliz

doi:10.1177/1933719115578924

Cited by 44 publications

(39 citation statements)

References 47 publications

(52 reference statements)

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“…These changes are increasingly viewed as a consequence of genetic or epigenetic polymorphism (154,(188)(189)(190). Other epigenetic changes (191)(192)(193)(194)(195)(196) comprise methylation, demethylation of DNA and modifications in histone code (193,197,198).…”

Section: Figurementioning

confidence: 99%

Pathogenesis of endometriosis: the genetic/epigenetic theory

Koninckx

Ussia

Adamyan

et al. 2019

Fertility and Sterility

274

187

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Objective: To study the pathophysiology of endometriosis. Design: Overview of observations on endometriosis. Setting: Not applicable. Patient(s): None. Interventions(s): None. Main Outcome Measure(s): The hypothesis is compatible with all observations. Result(s): Endometriosis, endometrium-like tissue outside the uterus, has a variable macroscopic appearance and a poorly understood natural history. It is a hereditary and heterogeneous disease with many biochemical changes in the lesions, which are clonal in origin. It is associated with pain, infertility, adenomyosis, and changes in the junctional zone, placentation, immunology, plasma, peritoneal fluid, and chronic inflammation of the peritoneal cavity. The Sampson hypothesis of implanted endometrial cells following retrograde menstruation, angiogenic spread, lymphogenic spread, or the metaplasia theory cannot explain all observations if metaplasia is defined as cells with reversible changes and an abnormal behavior/morphology due to the abnormal environment. We propose a polygenetic/polyepigenetic mechanism. The set of genetic and epigenetic incidents transmitted at birth could explain the hereditary aspects, the predisposition, and the endometriosis-associated changes in the endometrium, immunology, and placentation. To develop typical, cystic ovarian or deep endometriosis lesions, a variable series of additional transmissible genetic and epigenetic incidents are required to occur in a cell which may vary from endometrial to stem cells. Subtle lesions are viewed as endometrium in a different environment until additional incidents occur. Typical cystic ovarian or deep endometriosis lesions are heterogeneous and represent three different diseases. Conclusion(s): The genetic epigenetic theory is compatible with all observations on endometriosis. Implications for treatment and prevention are discussed. (Fertil Steril Ò 2019;111:327-40. Ó2018 by American Society for Reproductive Medicine.) El resumen está disponible en Español al final del artículo.

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Section: Figurementioning

confidence: 99%

Pathogenesis of endometriosis: the genetic/epigenetic theory

Koninckx

Ussia

Adamyan

et al. 2019

Fertility and Sterility

274

187

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“…Epigenetic changes, during fetal life (179), have become a focus of interest during the past decade (180)(181)(182)(183)(184). They comprise methylation and demethylation of DNA (181,185,186), modifications in the histone code in endometriosis tissue in comparison with the endometrium, and experimental modifications of the histone code in cell lines and animal species.…”

Section: Arguments Pointing To Genetic or Epigenetic Changesmentioning

confidence: 99%

Pathogenesis of deep endometriosis

Gordts

Koninckx²,

Brosens

2017

Fertility and Sterility

177

115

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“…One potential candidate that is suspected to be involved in epigenetic and post-translational modifications and EMT program in endometriosis is Enhancer of Zeste homolog 2 (EZH2), which was reported to be upregulated in endometriosis 23 .…”

Section: Introductionmentioning

confidence: 99%

Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis

Zhang

Dong

Liu

et al. 2017

Sci Rep

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EZH2, a subunit of the polycomb repressive complex 2 (PRC2) catalyzing trimethylation of histone H3 lysine 27 (H3K27), induces epithelial-mesenchymal transition (EMT) in cancers. However, whether EZH2 regulates EMT in endometriosis is unclear. Here, we show that EZH2 expression, along with its associated PRC2 proteins, is significantly elevated in ectopic and eutopic endometrium from women with endometriosis as compared with control endometrium. EZH2 knockdown or inhibition restored the epithelial phenotypes of endometriotic epithelial cells, concomitant with the upregulation of E-cadherin and downregulation of vimentin and transcription factors (Snail and Slug) as well as reduced cellular migratory and invasive propensity. Conversely, overexpression of EZH2 induced the expression of Snail, Slug and vimentin and suppresses E-cadherin expression. In vivo administration of 3-Deazaneplanocin A (DZNep), an EZH2 inhibitor, significantly inhibited the growth of endometriotic lesions and improved generalized hyperalgesia, along with attenuated EMT and reduced fibrosis in endometriosis. Notably, platelets induced EZH2 upregulation and increased H3K27 and H3K9 trimethylation levels in endometriotic epithelial cells. These data identify EZH2 as a novel driver of EMT in endometriosis, implicates the link between wound healing and epigenetic changes in the context of endometriosis, and underscore the role of platelets in the development of endometriosis.

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H3K27me3 is an Epigenetic Mark of Relevance in Endometriosis

Cited by 44 publications

References 47 publications

Pathogenesis of endometriosis: the genetic/epigenetic theory

Pathogenesis of endometriosis: the genetic/epigenetic theory

Pathogenesis of deep endometriosis

Enhancer of Zeste homolog 2 (EZH2) induces epithelial-mesenchymal transition in endometriosis

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