Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting 6–20% of reproductive-age women worldwide, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, often accompanied by insulin resistance and infertility. Emerging evidence suggests that environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), may contribute to PCOS pathogenesis. This study employs network toxicology and molecular docking to elucidate the mechanistic links between BPA exposure and PCOS. By integrating multi-database analyses, we identified 294 BPA-related targets and 67 shared targets with PCOS, including key genes (PPARG, HSP90AA1, IGF1R, and INSR) implicated in hormonal dysregulation, insulin resistance, and inflammation. Protein-protein interaction (PPI) networks and enrichment analyses revealed their involvement in critical pathways such as estrogen signaling, ovarian steroidogenesis, and PI3K-Akt signaling. Molecular docking confirmed stable binding between BPA and these targets, with IGF1R exhibiting the strongest affinity (− 8.0 kcal/mol). Validation using the GSE5090 dataset demonstrated significant upregulation of PPARG and HSP90AA1 in PCOS patients. Our findings suggest that BPA disrupts follicular development, exacerbates hyperandrogenism, and impairs metabolic homeostasis through multi-target interactions, providing novel insights into the environmental etiology of PCOS and potential therapeutic strategies. Validates BPA as modifiable risk factor for PCOS. Identifies four actionable molecular targets for therapy. Supports policy expansion for endocrine disruptor regulation. Establishes methodology for studying chemical-gene-disease interactions.
Peng et al. (Sat,) studied this question.