From embryo to sexual maturity: chronic BPA exposure under elevated contamination scenarios induces multi-organ toxicity in marine medaka (Oryzias melastigma).

Bisphenol A (BPA) is a widely distributed endocrine-disrupting chemical in aquatic environments, yet its long-term toxicological effects in marine fish remain insufficiently understood. In the present study, marine medaka (Oryzias melastigma) were chronically exposed to BPA from the embryonic stage to sexual maturity for 140 days, and multiple endpoints were integrated to evaluate developmental performance, adult behavior and growth, histopathological alterations, oxidative stress responses, gene-expression responses, and intestinal microbiota changes. The measured BPA concentrations were 40.4 and 161.9 μg/L. Chronic BPA exposure significantly reduced embryonic heart rate and hatching success at 161.9 μg/L. In adults, BPA exposure was associated with altered spontaneous locomotor activity, and body mass was significantly increased in males at the high concentration. Histopathological analyses revealed hepatocellular vacuolization and lipid accumulation, ovarian follicular atresia, testicular structural disorganization, and intestinal villus damage. In addition, BPA exposure weakened antioxidant defense capacity in a tissue- and sex-dependent manner, as reflected by significant reductions in selected SOD and GSH-Px endpoints. Gene expression analyses further showed treatment-associated changes in genes related to neural regulation, the hypothalamic-pituitary-gonadal (HPG) axis, hepatic estrogen responsiveness, and intestinal immune and oxidative stress regulation. Moreover, chronic BPA exposure altered intestinal microbial community structure, with females showing more pronounced dysbiosis than males. Overall, these findings characterize the chronic multi-organ hazards of BPA in marine medaka under elevated contamination scenarios.