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The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights

1
Department of Obstetrics and Gynecology, “Filippo Del Ponte” Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy
2
Department of Gynecology and Obstetrics, Münster University Hospital, D-48149 Münster, Germany
3
Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 60, 20136 Milan, Italy
4
Department of Obstetrics and Gynecology, AOUI Verona, University of Verona, Piazzale Aristide Stefani 1, 37126 Verona, Italy
5
School of Medicine, University of Tennessee Health Science Center, 910 Madison Ave, Memphis, TN 38163, USA
6
Virginia Commonwealth University, 907 Floyd Ave, Richmond, VA 23284, USA
*
Author to whom correspondence should be addressed.
Equal contributions (joint first authors).
Int. J. Mol. Sci. 2019, 20(22), 5615; https://doi.org/10.3390/ijms20225615
Received: 2 October 2019 / Revised: 1 November 2019 / Accepted: 7 November 2019 / Published: 10 November 2019
(This article belongs to the Special Issue Endometriosis Research: From Bench to Bedside)
The etiopathogenesis of endometriosis is a multifactorial process resulting in a heterogeneous disease. Considering that endometriosis etiology and pathogenesis are still far from being fully elucidated, the current review aims to offer a comprehensive summary of the available evidence. We performed a narrative review synthesizing the findings of the English literature retrieved from computerized databases from inception to June 2019, using the Medical Subject Headings (MeSH) unique ID term “Endometriosis” (ID:D004715) with “Etiology” (ID:Q000209), “Immunology” (ID:Q000276), “Genetics” (ID:D005823) and “Epigenesis, Genetic” (ID:D044127). Endometriosis may origin from Müllerian or non-Müllerian stem cells including those from the endometrial basal layer, Müllerian remnants, bone marrow, or the peritoneum. The innate ability of endometrial stem cells to regenerate cyclically seems to play a key role, as well as the dysregulated hormonal pathways. The presence of such cells in the peritoneal cavity and what leads to the development of endometriosis is a complex process with a large number of interconnected factors, potentially both inherited and acquired. Genetic predisposition is complex and related to the combined action of several genes with limited influence. The epigenetic mechanisms control many of the processes involved in the immunologic, immunohistochemical, histological, and biological aberrations that characterize the eutopic and ectopic endometrium in affected patients. However, what triggers such alterations is not clear and may be both genetically and epigenetically inherited, or it may be acquired by the particular combination of several elements such as the persistent peritoneal menstrual reflux as well as exogenous factors. The heterogeneity of endometriosis and the different contexts in which it develops suggest that a single etiopathogenetic model is not sufficient to explain its complex pathobiology. View Full-Text
Keywords: endometriosis; pathogenesis; genetics; epigenetics; immunology endometriosis; pathogenesis; genetics; epigenetics; immunology
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Laganà, A.S.; Garzon, S.; Götte, M.; Viganò, P.; Franchi, M.; Ghezzi, F.; Martin, D.C. The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights. Int. J. Mol. Sci. 2019, 20, 5615.

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