{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:45:08Z","timestamp":1791845108817,"version":"4.3.4"},"reference-count":0,"publisher":"Association of Basic Medical Sciences of FBIH","issue":"11","license":[{"start":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:00:00Z","timestamp":1751241600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomol Biomed"],"abstract":"<jats:p>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder characterized by cystic ovarian morphology, anovulation, and infertility. Ovarian fibrosis has recently emerged as a key pathological feature of PCOS. This study investigated whether pirfenidone (PFD), an antifibrotic agent, could improve ovarian dysfunction in a letrozole-induced PCOS rat model. Forty-two female Wistar albino rats were divided into six groups (n=7 each): control, PFD, PCOS, PCOS\/PFD, PCOS\/combined oral contraceptives (COC), and PCOS\/PFD\/COC. PCOS was induced using letrozole (1 mg\/kg\/day orally for 21 days). PFD (200 mg\/kg\/day) and\/or COC (0.18\u202fmg\/kg cyproterone acetate and 0.00315\u202fmg\/kg ethinyl estradiol) were administered for 21 days. Compared to controls, PCOS rats exhibited significant disruptions in estrous cyclicity, ovarian morphology, and fibrosis-related markers (all p&lt;0.0001), despite no significant changes in testosterone (p=0.058) or estrogen (p=0.896) levels. PFD treatment significantly improved estrous cyclicity, follicular profile, and corpora lutea count (all p&lt;0.0001), reduced ovarian fibrosis (p&lt;0.0001), downregulated TGF-\u03b21, CTGF, and MMP-9 (all p&lt;0.0001), and upregulated PPAR-\u03b3 and MMP-2 (both p&lt;0.0001), without affecting hormone levels (p=0.945 and p=0.479, respectively). COC treatment also improved estrous cyclicity and ovarian histology (all p&lt;0.0001), reduced fibrosis (p=0.005), and modulated TGF-\u03b21, CTGF, MMP-9, and PPAR-\u03b3 expression (p=0.0001 to &lt;0.0001), but had no effect on MMP-2 (p=0.868). Combination therapy (PCOS\/PFD\/COC) provided additional improvement in corpora lutea count (p&lt;0.0001 vs. PCOS\/PFD) and collagen deposition (p=0.002 vs. PCOS\/PFD) but did not confer further benefits in fibrosis-related marker expression or folliculogenesis (all p&gt;0.05). These findings suggest that pirfenidone mitigates PCOS pathology by targeting ovarian fibrosis, supporting antifibrotic therapy as a novel and promising approach.<\/jats:p>","DOI":"10.17305\/bb.2025.12676","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T18:00:43Z","timestamp":1751306443000},"page":"2558-2569","source":"Crossref","is-referenced-by-count":10,"title":["Pirfenidone reduces ovarian fibrosis and improves PCOS in letrozole-induced rat model"],"prefix":"10.17305","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2466-9417","authenticated-orcid":false,"given":"Ay\u015fe","family":"\u00c7ak\u0131r G\u00fcndo\u011fdu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neziha Senem","family":"Ar\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmet","family":"Ko\u00e7ak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9553-6021","authenticated-orcid":false,"given":"G\u00fclnihal","family":"\u015eenol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asiye","family":"H\u00f6bel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer","family":"Eldiven","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatih","family":"Kar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orhan","family":"\u00d6zatik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"6922","published-online":{"date-parts":[[2025,6,30]]},"container-title":["Biomolecules and Biomedicine"],"original-title":[],"link":[{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12676\/3946","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/download\/12676\/3946","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T22:03:58Z","timestamp":1761084238000},"score":1,"resource":{"primary":{"URL":"https:\/\/bjbms.org\/ojs\/index.php\/bjbms\/article\/view\/12676"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,30]]},"references-count":0,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,9,10]]}},"URL":"https:\/\/doi.org\/10.17305\/bb.2025.12676","relation":{},"ISSN":["2831-090X","2831-0896"],"issn-type":[{"value":"2831-090X","type":"electronic"},{"value":"2831-0896","type":"print"}],"subject":[],"published":{"date-parts":[[2025,6,30]]}}}