Background: Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used in polycarbonate plastics and epoxy resins. Prolonged exposure to BPA may impair ovarian function through oxidative stress, disruption of gonadotropin secretion, and altered expression of steroidogenic and folliculogenesis-related genes. This study investigated the molecular and biochemical mechanisms of BPA-induced ovarian dysfunction and evaluated the protective role of Withania somnifera (Ashwagandha).

Methods and Results: Forty sexually mature female Wistar rats were randomly allocated into four groups (n = 10/group): control, BPA (50 mg/kg/day, intraperitoneally), Ashwagandha (300 mg/kg/day, orally), and BPA + Ashwagandha for 30 consecutive days. Serum reproductive hormones, including FSH, LH, and testosterone, were measured. Oxidative stress was assessed by malondialdehyde (MDA) and total antioxidant capacity (TAC). Quantitative real-time PCR was used to evaluate ovarian expression of Ahr, Esr1, Cyp19a1, Fshr, Grin2b, and Anapc2, using Gapdh as the reference gene. BPA exposure significantly decreased FSH and increased LH and testosterone, indicating hypothalamic–pituitary–ovarian axis disruption. BPA also increased MDA and reduced TAC, reflecting oxidative imbalance. At the molecular level, BPA upregulated Ahr expression and downregulated Esr1, Cyp19a1, Fshr, Grin2b, and Anapc2. Co-treatment with Ashwagandha improved hormonal balance, reduced lipid peroxidation, restored antioxidant capacity, and normalized ovarian gene expression toward control values.

Conclusions: BPA induces ovarian dysfunction through oxidative stress, endocrine dysregulation, and AhR-associated transcriptional reprogramming. Ashwagandha mitigates these effects by enhancing antioxidant defense and restoring steroidogenic, estrogenic, and follicular regulatory pathways.