An update on epigenetic mechanisms in endometriosis.

Abstract

The etiopathogenesis of endometriosis, a chronic debilitating disease affecting nearly 10% of women, has evaded elucidation until the recent epigenetic discoveries. Although still deemed multifactorial, endometriosis is likely predisposed in women with genetic and epigenetic alterations, which are activated by environmental factors. There are many epigenetic changes that have recently been associated with endometriosis: DNA methylation and phosphorylation, modifications to histones and non-coding RNA, and chromatin remodeling and organization. Gene markers, such as HOXA10, SF-1, and GATA transcription factors, are also debatably correlated to endometriosis. An improved understanding of the etiopathogenesis of endometriosis may propel our field toward our objectives: sooner and more efficient detection as well as targeted therapy. In this comprehensive review, we will identify and discuss the current literature on epigenetic changes seen in endometriosis. A primary computerized search was performed on PubMed and Google scholar of publications from 1990 to 2022. We searched for keyword terms such as "endometriosis" and "endometriosis epigenetics." We also looked through the references of prior articles to find other relevant articles to this topic. Articles were categorized by type of epigenetic change found such as DNA hypo- or hyper- methylation, histone hyper- or hypo-acetylation, chromatin remodeling, and non-coding RNA-mediated down-regulation and the research was elaborated in sections based on the type of epigenetic change. There are many articles on TET, DNMTs, EZH2, HDACs, HATs, let-7 family, miRNAs, Hox proteins, GATA family, sirtuins (e.g. SIRT1, SIRT3), ARID1A, SF-1, USF1, USF2, STRA6, ESR1, ESR2, PGR, ALDHIA2, and CTCF; however, the studies analyzed in this review were heterogeneous in comparison populations, analysis methods, tissues types (e.g. endometriomas, ectopic endometriotic tissue, eutopic endometrial tissue). Due to this, it is difficult to synthesize over-arching conclusions based on the current literature; however, there are many epigenetic changes and genes linked to endometriosis as noted in the literature.