{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:57:05Z","timestamp":1790765825897,"version":"4.1.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Endometriosis is an estrogen-dependent chronic inflammatory disorder in which ectopic endometrial-like tissue undergoes repeated injury, incomplete resolution, and progressive remodeling. Fibrosis is therefore not merely a terminal scar but an active component of lesion biology. Cyclic bleeding activates platelets and innate immune cells, generates iron-dependent oxidative stress and hypoxia, and sustains transforming growth factor-\u03b2, sphingosine-1-phosphate, Wnt\/\u03b2-catenin, PI3K\/AKT\u2013ERK, and Notch-related signals. These cues promote fibroblast activation, myofibroblast differentiation, extracellular-matrix deposition, and epithelial-, endothelial-, mesothelial-, or macrophage-to-mesenchymal plasticity. The resulting stiff matrix can further reinforce inflammatory, vascular, and neural programs, creating a self-maintaining inflammation\u2013fibrosis circuit. Clinically, this circuit may stabilize ectopic lesions, promote adhesions, increase tissue tension and neurogenic inflammation, damage the ovarian cortex, and perturb the peritoneal and eutopic endometrial environments. These effects provide mechanistic links to persistent pain and infertility, although fibrosis is neither the sole determinant of symptoms nor a uniform feature across lesion phenotypes. This Mini Review integrates evidence from experimental models, human pathology, and single-cell studies; identifies uncertainties in cellular lineage, lesion chronology, and outcome attribution; and discusses therapeutic implications. Conventional hormonal and surgical treatment remains central, whereas antifibrotic, immunomodulatory, and complementary approaches require mechanism-based clinical validation. Progress will depend on standardized fibrosis phenotyping, longitudinal and spatial sampling, patient-derived multicellular models, and trials that align biological targets with pain, fertility, and recurrence outcomes.<\/jats:p>","DOI":"10.3389\/fmed.2026.1984591","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:57:10Z","timestamp":1790762230000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inflammation\u2013fibrosis crosstalk in endometriosis: immune\u2013stromal mechanisms linking lesion persistence to pain and infertility"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaofeng","family":"Liu","sequence":"first","affiliation":[{"name":"First College of Clinical Medicine, Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]},{"name":"Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Qu","sequence":"additional","affiliation":[{"name":"Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhong","family":"Gu","sequence":"additional","affiliation":[{"name":"Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Reproductive and Genetics Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuguang","family":"Fu","sequence":"additional","affiliation":[{"name":"Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University","place":["Qingdao, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1056\/NEJMra1810764","article-title":"Endometriosis","volume":"382","author":"Zondervan","year":"2020","journal-title":"N Engl J Med"},{"key":"B2","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41572-018-0008-5","article-title":"Endometriosis","volume":"4","author":"Zondervan","year":"2018","journal-title":"Nat Rev Dis Primers"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2807","DOI":"10.1016\/j.cell.2021.04.041","article-title":"Endometriosis: etiology, pathobiology, and 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