Epigenetic regulation of the pathological process in endometriosis

Abstract

BackgroundEndometriosis is one of the most common gynecological diseases that greatly compromises the quality of life in affected individuals. A growing body of evidence shows that the remodeling of retrograde endometrial tissues to the ectopic endometriotic lesions involves multiple epigenetic alterations, such as DNA methylation, histone modification, and microRNA expression.MethodsThis article retrospectively reviewed the studies that were related to the epigenetic regulatory factors that contribute to the development and maintenance of endometriosis. A literature search was performed in order to collect scientific articles that were written in English by using the key words of “endometriosis,” “epigenetics,” “DNA methylation,” “histone modification,” and “microRNA.”ResultsEpigenetic modifications, including DNA methylation, histone modification, and microRNA expression, are involved in the pathogenesis of endometriosis. These epigenetic players are regulated or tuned by microenvironmental cues, such as locally produced estradiol, proinflammatory cytokines, and hypoxic stress, and reciprocally regulate the process or response to those stimuli.ConclusionUnderstanding the molecular mechanisms that underlie these epigenetic regulatory processes would shed light on the etiology and/or progression of endometriosis and facilitate the development of novel therapeutic strategies.

Hypoxia: The force of endometriosis

“…Accumulating evidence indicates that endometriosis is an epigenetic disease . Despite the identical genetic background between eutopic and ectopic endometrial cells in patients with endometriosis, numerous studies reported that significant differences in the biochemical properties of these two tissues exist.…”

Epigenetics in disease etiopathogenesis

“…Inflammation induces DNMT3a expression and locus-specific hypermethylation. MiRNA-20a induced by hypoxia and miRNA302a induced by inflammatory cytokines both contribute to modulation of DNA methylation (HSIAO, et al 2017).…”

Molecular-genetic determinants of the development of endometriosis

“…Согласно современным представлениям, важное значение в развитии эндометриоза наряду с генетическими факторами играют и эпигенетические механизмы (уровень мети лирования ДНК, модификации гистоновых белков, регуляторные некодирующие РНК (non-coding RNAs)) [28][29][30][31][32][33][34][35][36].…”

“…При сравнительном исследовании эктопического и эутопического эндометрия выявлена связь модификации гистонов с продукцией белков HDAC1, SUV39H1, SUV39H2, G9a, некоторых изоформ HDAC5 в очагах эндометриоза [28,32,33]. В исследованиях последних лет установлена значимая роль в развитии эндометриоза некодирующих РНК (noncoding RNAs), в частности микро-РНК (miRNAs) [34][35][36]. Эти РНК участвуют в регуляции воздействия стероидных гормонов на эндометрий.…”

“…Следует отметить, что через микро-РНК реализуются патогенетические эффекты дифференциального метилирования ДНК, а также гипоксии и воспаления при развитии эндометриоза [36]. Так, при гиперметилировании ДНК подавляется образование микро-РНК (miR-196b, miR-503, miR-23 a/b), а гипоксия и воспаление, наоборот, индуцируют синтез микро-РНК (miR-148а, miR-20а, miR-302а), что изменяет продукцию определенных таргетных белков (MYC, BCL-2,SF-1, DNMT1 и др.)…”