{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:47:09Z","timestamp":1790128029279,"version":"4.0.1"},"reference-count":149,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Endometriosis (EM) is a chronic, estrogen-dependent inflammatory disorder affecting approximately 6\u201310% of women of reproductive age in the general population and remains a major cause of chronic pelvic pain and infertility. High recurrence rates and enduring symptoms despite current treatments underscore the need for a more thorough understanding of its intricate biology. There is growing evidence that the interaction among oxidative stress (OS), microbiome dysbiosis, and epigenetic dysregulation contributes to immunological activation, hormonal imbalance, and the persistence of ectopic lesions. Important disease mechanisms, such as progesterone resistance, inflammatory signaling, and aberrant cellular proliferation, are influenced by epigenetic changes, which include aberrant DNA methylation, histone modifications, and dysregulated non-coding RNAs. Simultaneously, high levels of reactive oxygen species (ROS) reinforce lesion survival and chronic inflammation by promoting angiogenesis, fibrosis, and tissue damage. Changes in the microbiome also affect immunological responses, oxidative balance, estrogen metabolism, and epigenetic control, indicating the existence of interrelated pathogenic loops. This narrative review presents an integrated mechanistic framework for endometriosis, summarizing the available data that connect these pathways. Furthermore, the growing implications of non-invasive biomarkers and precision medicine techniques highlight the potential for improved diagnosis, disease classification, and targeted treatment approaches.<\/jats:p>","DOI":"10.3390\/jpm16060299","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T17:11:01Z","timestamp":1780333861000},"page":"299","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Epigenetics, Oxidative Stress, and the Microbiome in Endometriosis: Toward an Integrated Mechanistic Framework for Precision Medicine"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3036-7212","authenticated-orcid":false,"given":"Nektaria","family":"Zagorianakou","sequence":"first","affiliation":[{"name":"Scientific Laboratory for Innovative Technologies in Internal Medicine, Department of Nursing, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-9981-7488","authenticated-orcid":false,"given":"Stylianos","family":"Makrydimas","sequence":"additional","affiliation":[{"name":"Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3333-2620","authenticated-orcid":false,"given":"Efthalia","family":"Moustakli","sequence":"additional","affiliation":[{"name":"Department of Nursing, School of Health Sciences, University of Ioannina, 45500 Ioannina, Greece"},{"name":"Human Computer Interaction Laboratory, Department of Informatics and Telecommunications, University of Ioannina, 47150 Arta, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9227-1365","authenticated-orcid":false,"given":"Emmanouil D.","family":"Oikonomou","sequence":"additional","affiliation":[{"name":"Human Computer Interaction Laboratory, Department of Informatics and Telecommunications, University of Ioannina, 47150 Arta, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3904-7175","authenticated-orcid":false,"given":"Ioannis","family":"Mitrogiannis","sequence":"additional","affiliation":[{"name":"Harris Birthright Research Centre for Fetal Medicine, King\u2019s College London, London SE5 8BB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Sintou","sequence":"additional","affiliation":[{"name":"Department of Anesthesia, Patras University Hospital, 26504 Patras, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Makrydimas","sequence":"additional","affiliation":[{"name":"Department of Obstetrics & Gynecology, University Hospital of Ioannina, 45500 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"ref_1","unstructured":"Tsamantioti, E.S., and Mahdy, H. 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