Integrated metabolomic and histopathological analysis of renal alterations in mice following chronic bisphenol A (BPA) exposure

BPA is a widespread environmental contaminant with endocrine-disrupting properties, but its impact on renal metabolism remains incompletely understood. This study aimed to characterize metabolic alterations in mouse kidney following chronic BPA exposure and to relate these findings to histopathological changes. Mice were exposed to BPA at the lowest observed adverse effect level (50 mg/kg body weight/day) for 3 months, and kidney samples were analyzed using untargeted liquid chromatography-mass spectrometry-based metabolomics. BPA exposure was associated with distinct changes in renal metabolic profiles, particularly in pathways related to lipid metabolism, fatty acid oxidation, steroid metabolism, and xenobiotic biotransformation. Altered levels of polyunsaturated fatty acids and lysophospholipids suggested disruption of lipid homeostasis and membrane composition. Changes in acylcarnitine profiles were consistent with alterations in energy metabolism, while shifts in steroid metabolites indicated perturbations in steroidogenic pathways. Increased levels of conjugated metabolites suggested activation of phase II detoxification processes. Histopathological analysis revealed structural abnormalities, including tubular epithelial damage and glomerular alterations. Together, these findings provide a comprehensive overview of metabolic and structural changes in the kidney associated with chronic BPA exposure and highlight potential links between environmental toxicants and renal metabolic disturbances.