Epigenetic Factors in Eutopic Endometrium in Women with Endometriosis and Infertility

Abstract

Eutopic endometrium in patients with endometriosis is characterized by aberrant expression of essential genes during the implantation window. It predisposes to disturbance of endometrial receptivity. The pathomechanism of implantation failures in women with endometriosis remains unclear. This paper aims to summarize the knowledge on epigenetic mechanisms in eutopic endometrium in the group of patients with both endometriosis and infertility. The impaired DNA methylation patterns of gene promoter regions in eutopic tissue was established. The global profile of histone acetylation and methylation and the analysis of selected histone modifications showed significant differences in the endometrium of women with endometriosis. Aberrant expression of the proposed candidate genes may promote an unfavorable embryonic implantation environment of the endometrium due to an immunological dysfunction, inflammatory reaction, and apoptotic response in women with endometriosis. The role of the newly discovered proteins regulating gene expression, i.e., TET proteins, in endometrial pathology is not yet completely known. The cells of the eutopic endometrium in women with endometriosis contain a stable, impaired methylation pattern and a histone code. Medication targeting critical genes responsible for the aberrant gene expression pattern in eutopic endometrium may help treat infertility in women with endometriosis.

Keywords: DNA methylation; TET protein; endometrial receptivity; endometriosis; epigenetics; eutopic endometrium; histone modifications; implantation; infertility.

Figure 1

The epigenetic background of implantation failures in the pathogenesis of endometriosis-related infertility. Targets of epigenetic therapy in infertile women with endometriosis. DNMT—DNA methyltransferase, HDAC—histone deacetylase, TET1—ten-eleven-translocation 1 protein.