Systems Toxicology of Bisphenol A: Mechanistic Overlap in Metabolic and Reproductive Disruption

Bisphenol A (BPA), a high-production volume synthetic compound widely used in plastics and a range of consumer products, is recognized as a dual-action xenobiotic with endocrine-disrupting and obesogenic properties. This review synthesizes current evidence linking BPA exposure to two major public health issues: obesity and reproductive dysfunction, through disruption of shared molecular, cellular, and hormonal pathways. BPA disrupts metabolic homeostasis by altering energy balance, adipogenesis, lipid metabolism, and insulin signaling. Concurrently, it interferes with reproductive health through modulation of estrogen receptor signaling, steroidogenesis, and gonadal function. These shared pathways suggest a mechanistic convergence between endocrine and metabolic disruption. We further examine the environmental persistence of BPA, its widespread sources, major human exposure routes, and its potential for bioaccumulation in biological tissues and ecosystems. Evidence from animal models, epidemiological data, and in vitro studies supports the classification of BPA as a multifaceted xenobiotic capable of impairing multiple organ systems. Additionally, we discuss convergent pathways in BPA-mediated systemic toxicity, advances in identifying candidate biomarkers and cellular targets of BPA, research gaps, and future directions. This review emphasizes the need for integrated approaches in public health, toxicology, and environmental safety. It also underscores the importance of toxicological and therapeutic research to better understand BPA's systemic effects and strengthen more strategic future public health interventions.