{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:43:19Z","timestamp":1792813399064,"version":"4.5.0"},"reference-count":163,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Ovarian fibrosis is increasingly recognized as a pivotal factor contributing to ovarian ageing, dysfunction, and female infertility. It results from chronic or repetitive ovarian injury, such as that caused by repeated ovulation, which induces inflammation and excessive extracellular matrix (ECM) deposition, predominantly by activated fibroblasts and myofibroblasts. The key molecular pathways driving ovarian fibrosis include transforming growth factor-beta (TGF-\u03b2)\/Smad signalling, Wnt\/\u03b2-catenin, and PI3K\/Akt pathways, which orchestrate fibroblast activation, ECM remodelling, and tissue stiffening. Elevated collagen types I and III, fibronectin, and hyaluronan characterize the fibrotic ovarian stroma, disrupting normal folliculogenesis and steroidogenesis. Ovarian fibrosis is also implicated in reproductive pathologies such as polycystic ovary syndrome, premature ovarian insufficiency and endometriosis, and may contribute to an increased risk of ovarian cancer, although definitive causal links require further elucidation. Current therapeutic strategies remain largely experimental, focusing on antifibrotic agents such as pirfenidone, TGF-\u03b2 inhibitors, and modulation of oxidative stress, alongside emerging interventions such as stem cell therapies, which are offer potential avenues for intervention in the ovary. This review synthesizes current insights into the cellular and molecular mechanisms driving ovarian fibrosis, its association with reproductive disorders, and emerging therapeutic strategies. It underscores key knowledge gaps and emphasizes the need for future research focused on fibroblast activation, inflammatory signalling, and immune-ECM interactions to facilitate the development of targeted, long-term interventions aimed at preventing or reversing ovarian fibrosis and preserving female fertility.<\/jats:p>","DOI":"10.1093\/molehr\/gaaf058","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:05:42Z","timestamp":1764162342000},"source":"Crossref","is-referenced-by-count":24,"title":["Molecular mechanisms of ovarian fibrosis"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-1962-1128","authenticated-orcid":false,"given":"Beyza Gaye","family":"Edepli","sequence":"first","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Yeditepe University , Istanbul,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6781-9983","authenticated-orcid":false,"given":"Aylin","family":"Yaba","sequence":"additional","affiliation":[{"name":"Department of Histology and Embryology, Faculty of Medicine, Yeditepe University , Istanbul,","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"2026010710482244600_gaaf058-B1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.actbio.2025.05.035","article-title":"Collagen fiber density observed in metastatic ovarian cancer promotes tumor cell adhesion","volume":"200","author":"Abbaspour","year":"2025","journal-title":"Acta Biomater"},{"key":"2026010710482244600_gaaf058-B2","doi-asserted-by":"crossref","first-page":"3053","DOI":"10.3390\/cells10113053","article-title":"TRPV4 mechanotransduction in 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