Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis
Open Access
- 7 January 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Stem Cell Reviews and Reports
- Vol. 17 (4), 1174-1193
- https://doi.org/10.1007/s12015-020-10115-5
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. Graphical AbstractKeywords
This publication has 189 references indexed in Scilit:
- Mig6 Is a Sensor of EGF Receptor Inactivation that Directly Activates c-Abl to Induce Apoptosis during Epithelial HomeostasisDevelopmental Cell, 2012
- Progesterone receptors, their isoforms and progesterone regulated transcriptionMolecular and Cellular Endocrinology, 2012
- miRNAs and estrogen actionTrends in Endocrinology & Metabolism, 2012
- Alterations in progesterone receptor membrane component 2 (PGRMC2) in the endometrium of macaques afflicted with advanced endometriosisMolecular Human Reproduction, 2012
- Tissue physiology and pathology of aromataseSteroids, 2012
- mRNA-Expression of ERα, ERβ, and PR in Clonal Stem Cell Cultures Obtained from Human Endometrial BiopsiesThe Scientific World Journal, 2011
- The role of the Hoxa10/HOXA10 gene in the etiology of endometriosis and its related infertility: a reviewJournal of Assisted Reproduction and Genetics, 2010
- Molecular Mechanisms of Treatment Resistance in Endometriosis: The Role of Progesterone–Hox Gene InteractionsSeminars in Reproductive Medicine, 2010
- Estrogen Receptor-β, Estrogen Receptor-α, and Progesterone Resistance in EndometriosisSeminars in Reproductive Medicine, 2010
- MicroRNAs: Target Recognition and Regulatory FunctionsCell, 2009