Emerging evidence for skeletal muscle as a target of BPA exposure

Endocrine disruptors are exogenous chemicals that interfere with hormonal signaling, and among them, bisphenol-A (BPA) is one of the most widely used and globally prevalent. Human exposure to BPA occurs through multiple routes, and measurable levels are detected in the majority of biological samples worldwide. At the molecular level, BPA interacts with several nuclear and membrane receptors, conferring estrogenic and anti-androgenic properties that disrupt endocrine, metabolic, and cardiovascular systems. Although the biological effects of BPA have been extensively studied in reproductive, neural, hepatic, and adipose tissues, its impact on skeletal muscle has been comparatively understudied, despite the central role of this tissue in glucose homeostasis and energy metabolism. In addition, direct human evidence specifically linking BPA exposure to skeletal muscle structure or function remains limited. This review summarizes current evidence regarding the effects of BPA on skeletal muscle structure and function. Experimental studies indicate that BPA disrupts insulin signaling in skeletal muscle by impairing insulin receptor-dependent pathways, reducing Akt phosphorylation and GLUT4 translocation, and promoting inflammatory responses, ultimately leading to insulin resistance and glucose intolerance. Developmental exposure to BPA further alters muscle fiber composition, gene expression, calcium signaling, and excitation-contraction coupling, with persistent effects on muscle phenotype and function. Collectively, the findings reviewed here identify skeletal muscle as a critical, yet underrecognized, target of BPA toxicity and underscore the need for future studies addressing chronic low-dose exposure and long-term outcomes, particularly in human populations.