Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Abstract

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis.

Analysis of Competitive Endogenous Mechanism and Survival Prognosis of Serum Exosomes in Ovarian Cancer Patients Based on Sequencing Technology and Bioinformatics

“…Frontiers in Genetics | www.frontiersin.org June 2022 | Volume 13 | Article 850089 Sarkargar et al, 2021;Szukiewicz et al, 2021). Many studies have demonstrated the influence of genetic and epigenetic modifications on tumor initiation and progression in ovarian cancer, endometrial cancer, and cervical cancer.…”

Expression and significance of estrogen receptor and progesterone receptor in endometrial tissue of patients with intrauterine adhesions

“…It is reported in the literature that ovarian hormones directly affect the function of the endometrium, and estrogen is a key factor to promote the regeneration and repair of the endometrium and regulate menstruation (12). Progesterone is an important steroid hormone in the body, which interacts with estrogen and periodically acts on the endometrium (13,14). ER and PR are important substances in the female endocrine system, both expressed in the uterus and highly expressed in the endometrium (15).…”

Pathogenesis of Endometriosis: The Origin of Pain and Subfertility

“…For example, dioxin, an omnipresent pollutant, is described as interfering with estrogen signaling through epigenetic modulation [33]. The first experimental data in animal models show an alteration in disease progression by epigenetic modulation, a fact that could be used as a new treatment approach [34,35]. Another still-experimental aspect is the analysis of EM-specific exosomes.…”