Pirfenidone reduces ovarian fibrosis and improves PCOS in letrozole-induced rat model
Yazarlar (8)
Prof. Dr. Ayşe GÜNDOĞDU Sinop Üniversitesi, Türkiye
Dr. Öğr. Üyesi Neziha Senem Arı Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Dr. Öğr. Üyesi Ahmet Koçak Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Arş. Gör. Gülnihal Şenol Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Asiye Höbel Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Ömer Eldiven
Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Fatih Kar Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
Orhan Özatik Kütahya Sağlık Bilimleri Üniversitesi, Türkiye
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | Biomolecules and Biomedicine (Q3) | ||
| Dergi ISSN | 2831-0896 Dergi Bilgileri (2025) | ||
| Makale Dili | İngilizce | Basım Tarihi | 09-2025 |
| Kabul Tarihi | – | Yayınlanma Tarihi | 30-06-2025 |
| Cilt / Sayı / Sayfa | 25 / 11 / 2558–2569 | DOI | 10.17305/bb.2025.12676 |
| Makale Linki | https://www.bjbms.org/ojs/index.php/bjbms/article/download/12676/3946 | ||
| UAK Araştırma Alanları |
Ziraat, Orman ve Su Ürünleri
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| Özet |
| 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 in each group): control, PFD, PCOS, PCOS/PFD, PCOS/combined oral contraceptives (COCs), 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 mg/kg cyproterone acetate and 0.00315 mg/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 < 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 < 0.0001), reduced ovarian fibrosis (P < 0.0001), downregulated transforming growth factor-beta 1 (TGF-β1), connective tissue growth factor (CTGF), and matrix metallopeptidase (MMP)-9 (all P < 0.0001), and upregulated peroxisome proliferator-activated receptor-gamma (PPAR-γ) and MMP-2 (both P < 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 < 0.0001), reduced fibrosis (P = 0.005), and modulated TGF-β1, CTGF, MMP-9, and PPAR-γ expression (P = 0.0001 to <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 < 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 > 0.05). These findings suggest that PFD mitigates PCOS pathology by targeting ovarian fibrosis, supporting antifibrotic therapy as a novel and promising approach. |
| Anahtar Kelimeler |
| COCs | combined oral contraceptives | ovarian fibrosis | PCOS | PFD | pirfenidone | Polycystic ovary syndrome | TGF-β1 | transforming growth factor-beta 1 |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Scopus | 7 |