{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T05:08:58Z","timestamp":1778476138608,"version":"3.51.4"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"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. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endometriosis is a chronic, estrogen-dependent inflammatory disorder and a leading cause of female infertility. Ovarian endometriomas, a common manifestation of endometriosis, are commonly associated with diminished ovarian function; however, the mechanisms underlying endometrioma-induced follicular dysregulation remain poorly understood. Thus, we aimed to determine whether endometrioma fluid (EmF) compromises preantral follicle development via oxidative stress and tissue fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EmF was collected from six patients during laparoscopic cystectomy or transvaginal ethanol sclerotherapy for endometriomas. Large preantral follicles (diameter: 130\u2013160 \u00b5m) were isolated from 14-day-old rats and cultured in the presence or absence of 0.5% EmF and 10 ng\/mL follicle-stimulating hormone (FSH). Follicular growth, steroidogenesis, and the expression of granulosa cell (GC) and theca cell (TC) markers were evaluated using morphometric analysis, hormone assays, and quantitative real-time PCR. Oxidative stress and fibrosis were assessed by measuring intracellular reactive oxygen species (ROS) levels and by performing immunostaining for fibrosis markers. In addition, the potential protective effects of pharmacological agents, including antioxidants, antifibrotic drugs, iron chelators, and androgens, were investigated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>EmF inhibited GC proliferation, suppressed FSH-induced estradiol production, and downregulated the expression of FSH receptor, anti-M\u00fcllerian hormone, and aromatase. Conversely, EmF promoted TC proliferation while downregulating LH receptor expression and androgenic enzyme levels. EmF also increased ROS generation in GC and induced the expression of the fibrotic markers, including transforming growth factor beta 1 and collagen type III, in TC. Androgen supplementation partially restored GC proliferation and FSH receptor expression, whereas antioxidants, antifibrotic agents, and iron chelators showed no significant effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>EmF disrupts preantral follicle development by inducing oxidative stress in GC and promoting fibrosis in TC, thereby impairing GC\u2013TC crosstalk. These findings reveal a novel pathogenic mechanism underlying endometrioma-associated infertility and underscore the need for therapeutic strategies targeting both oxidative stress and fibrotic remodeling within the ovaries.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1679042","type":"journal-article","created":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T04:25:34Z","timestamp":1778473534000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Negative impacts of ovarian endometrioma on preantral follicle development: implications for endometriosis-related infertility"],"prefix":"10.3389","volume":"17","author":[{"given":"Makoto","family":"Orisaka","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui","place":["Fukui, 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Gynecology, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hideaki","family":"Tsuyoshi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medical Sciences, University of Fukui","place":["Fukui, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Mizutani","sequence":"additional","affiliation":[{"name":"Department of Nursing, Faculty of Nursing and Welfare Sciences, Fukui Prefectural University","place":["Fukui, Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin K.","family":"Tsang","sequence":"additional","affiliation":[{"name":"Inflammation and Chronic Disease Program, Ottawa Hospital Research Institute","place":["Ottawa, ON, Canada"]},{"name":"Departments of Obstetrics and Gynecology & Cellular and Molecular Medicine, University of Ottawa","place":["Ottawa, ON, 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