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DNA methylomes of the adhesion sites, non\u2010adhesion sites, and blueberry spots were compared with those of ovary, endometrium, and peritoneum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The non\u2010adhesion sites showed an ovarian surface epithelium\u2010like structure near the adhesion site, which continued to a columnar epithelium\u2010like structure. Calretinin staining was strong in the ovarian surface epithelium\u2010like structure but weak in the columnar epithelium\u2010like structure. Estrogen receptors were absent in the ovarian surface epithelium\u2010like structure, but present in the columnar epithelium\u2010like structure. The adhesion sites had endometrial gland\u2010like structures that expressed estrogen receptors. Analyses of DNA methylomes classified the non\u2010adhesion sites and ovaries into the same group, suggesting that ovarian endometriomas originate from the ovarian surface epithelium. The adhesion sites, blueberry spots and peritoneum were classified in the same group, suggesting that the adhesion sites and blueberry spots originate from the peritoneum.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The present results support the invagination theory. Ovarian endometriomas consist of invaginated ovarian surface epithelium with celomic metaplasia and endometrium implants on the peritoneum.<\/jats:p><\/jats:sec>","DOI":"10.1002\/rmb2.12548","type":"journal-article","created":{"date-parts":[[2023,12,15]],"date-time":"2023-12-15T06:27:57Z","timestamp":1702621677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Combined histological and DNA methylome profiling approaches may provide insights into the pathophysiology of ovarian endometriomas"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0923-376X","authenticated-orcid":false,"given":"Ryo","family":"Maekawa","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Yamaguchi University Graduate School of Medicine  Ube 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