Taxifolin protects ovarian tissue from methotrexate-induced injury by targeting TGF-β/BMP-7 pathways

This study aimed to evaluate the protective effect of taxifolin on methotrexate (MTX)-induced ovarian toxicity in a rat model. Given the increasing clinical use of MTX and its known detrimental effects on ovarian function, identifying effective protective strategies is crucial for fertility preservation. Taxifolin, a potent natural antioxidant, was investigated for its potential to mitigate oxidative damage and maintain follicular integrity. Thirty adult female Wistar albino rats were randomly assigned to three groups (n = 10 each): Control, MTX, and MTX + Taxifolin. Ovarian injury was induced via a single intraperitoneal injection of MTX (20 mg/kg). The Taxifolin group received 50 mg/kg/day of taxifolin by oral gavage for 21 days post-MTX administration. Plasma malondialdehyde (MDA), anti-Müllerian hormone (AMH), and tumor necrosis factor-alpha (TNF-α) levels were assessed by ELISA. Ovarian tissue levels of bone morphogenetic protein-7 (BMP-7) and transforming growth factor-beta (TGF-β) were measured, and histopathological evaluations of follicle counts and stromal fibrosis were performed. Primordial (p < 0.001), primary (p = 0.001), secondary (p < 0.001), and tertiary (p < 0.001) follicle counts were significantly reduced in the MTX group compared to controls but improved with taxifolin treatment (p < 0.01 or p < 0.001). Ovarian fibrosis significantly increased with MTX (p < 0.001) and was attenuated by taxifolin (p < 0.001). Biochemically, MTX elevated plasma MDA (p < 0.001) and TNF-α (p < 0.001) levels and reduced AMH (p < 0.001) and BMP-7 (p < 0.001) while increasing TGF-β (p < 0.001). Taxifolin significantly reversed these biochemical alterations (p < 0.01 or p < 0.001). Taxifolin mitigates MTX-induced ovarian damage by reducing oxidative stress, inflammation, and fibrosis while preserving follicular development. These findings suggest taxifolin as a potential therapeutic agent for protecting ovarian function during MTX therapy.