Resveratrol improves follicular development in PCOS rats by inhibiting the inflammatory response and pyroptosis of granulosa cells

Chronic inflammation is a key characteristic of polycystic ovary syndrome (PCOS) and is associated with follicular dysplasia in PCOS. PCOS patients treated with 1000 mg resveratrol (RES) daily for 3 months showed significant improvement in menstrual cycle regularity compared to the placebo group. This investigation explores potential impact of RES on a rat model of PCOS. Sprague-Dawley (SD) rats were subjected to a 30-day letrozole/high-fat diet interventions for PCOS model establishment, followed by RES intervention (20 mg/kg/d) for an additional 30 days. RES intervention mitigated obesity, estrous cycle irregularities, and ovulation disorders while decreasing serum testosterone and lipopolysaccharide (LPS) levels in PCOS rats. Concurrently, inflammatory markers (TNF-α, NLPR3, IL-6,) and pyroptosis-related markers (GSDMD, cleaved-Caspase-1, IL-1β, IL-18) were downregulated. Additionally, KGN cells (a human granulosa-like cell line) were treated with LPS and RES for in vitro assays. It was observed that RES (15 μM) significantly reduced ROS production and downregulated inflammatory cytokine expression in LPS-intervened KGN cells. Additionally, RES downregulated the expression levels of pyroptosis-related factors (GSDMD and cleaved-Caspase-1) and attenuated IL-18 and IL-1β secretion in LPS-induced KGN cells. Furthermore, RES intervention improved the pyroptosis-associated morphology of KGN cells after LPS treatment. In conclusion, RES may restore follicular development in PCOS rats by inhibiting inflammation and NLRP3/GSDMD/Caspase-1-mediated pyroptosis of ovarian granulosa cells, providing new insights into potential therapeutic approaches for PCOS.