Dietary Bisphenol-A Exposure Induces Oxidative Stress-Mediated Developmental Renal Toxicity in Drosophila melanogaster.

BPA is an endocrine-disrupting molecule that is ubiquitously found in the environment. Epidemiological studies have shown that BPA exposure to humans during the early stage life is linked to renal dysfunction, including albuminuria, proteinuria, increased serum creatinine, and electrolyte imbalances. BPA alters the endocrine axis; however, BPA-mediated endocrine disruption has already been documented, and its cellular mechanism underlying developmental toxicity is not well defined. In the present study, we examined the effect of dietary BPA exposure on the developing renal organs of Drosophila larvae. BPA exposure significantly elevated ROS and lipid peroxidation, and depletion of key antioxidant enzymes, including SOD, CAT, and GSH, was observed, along with mitochondrial dysfunction, including a reduction in MMP and ATP levels, which indicate impaired bioenergetic capacity. Structural analyses revealed the disruption of cytoskeletal proteins F-actin and dlg, as well as progressive tubule hypertrophy. At the molecular level, transcriptional elevation of components related to the Nrf2-mediated stress response was observed, while transporter genes showed altered expression patterns, suggesting impaired detoxification capacity. Altogether, these findings demonstrate that early-stage exposure to BPA induces oxidative stress-associated mitochondrial dysfunction, transporter dysregulation, and cytoskeletal remodeling in MTs. Collectively, these results define oxidative stress-associated molecular, cellular and structural alterations underlying BPA-induced nephrotoxicity and demonstrate Drosophila as a mechanistically informative model for developmental toxicology research.