{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T14:50:16Z","timestamp":1792421416913,"version":"4.5.0"},"reference-count":364,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2019,11,10]],"date-time":"2019-11-10T00:00:00Z","timestamp":1573344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 \u201cEndometriosis\u201d (ID:D004715) with \u201cEtiology\u201d (ID:Q000209), \u201cImmunology\u201d (ID:Q000276), \u201cGenetics\u201d (ID:D005823) and \u201cEpigenesis, Genetic\u201d (ID:D044127). Endometriosis may origin from M\u00fcllerian or non-M\u00fcllerian stem cells including those from the endometrial basal layer, M\u00fcllerian 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.<\/jats:p>","DOI":"10.3390\/ijms20225615","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T04:07:07Z","timestamp":1573531627000},"page":"5615","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":400,"title":["The Pathogenesis of Endometriosis: Molecular and Cell Biology Insights"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1543-2802","authenticated-orcid":false,"given":"Antonio Simone","family":"Lagan\u00e0","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cFilippo Del Ponte\u201d Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5840-699X","authenticated-orcid":false,"given":"Simone","family":"Garzon","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cFilippo Del Ponte\u201d Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2360-2496","authenticated-orcid":false,"given":"Martin","family":"G\u00f6tte","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, M\u00fcnster University Hospital, D-48149 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Vigan\u00f2","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Laboratory, Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Via Olgettina 60, 20136 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Franchi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, AOUI Verona, University of Verona, Piazzale Aristide Stefani 1, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Ghezzi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, \u201cFilippo Del Ponte\u201d Hospital, University of Insubria, Piazza Biroldi 1, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1904-1449","authenticated-orcid":false,"given":"Dan C.","family":"Martin","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Tennessee Health Science Center, 910 Madison Ave, Memphis, TN 38163, USA"},{"name":"Virginia Commonwealth University, 907 Floyd Ave, Richmond, VA 23284, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nrendo.2013.255","article-title":"Endometriosis: Pathogenesis and treatment","volume":"10","author":"Vercellini","year":"2014","journal-title":"Nat. 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