Developmental bisphenol A exposure alters adipose metabolism and lipid remodeling in female mouse offspring

Bisphenol A (BPA), an endocrine-disrupting chemical widely detected in human populations, has been implicated in metabolic disorders following early-life exposure. However, the long-term effects of developmental BPA exposure on adipose metabolism under post-weaning dietary challenge remain incompletely understood. Pregnant C57BL/6J mice received BPA in drinking water at a maternal nominal target exposure of 50 μg/kg/day from gestational day 6 to postnatal day 21. After weaning, offspring were fed a normal diet or high-fat diet and evaluated at PND22, PND36, and PND91. Body weight, adipose morphology, serum biochemical parameters, hepatic histology, metabolic gene expression, untargeted lipidomics, and targeted ceramide profiles were assessed. BPA-associated alterations were more pronounced in females. BPA exposure was associated with reduced adipose expansion under high-fat feeding, reflected by smaller adipocytes and lower fat depot-to-body weight ratios, together with stage- and depot-dependent changes in adipose metabolic gene expression. Lipidomic analyses revealed alterations in glycerophospholipid composition, while targeted profiling identified depot-specific changes in ceramide species and the 24:1 ceramide/dihydroceramide ratio. Female offspring also showed stage-dependent hepatic morphological and aminotransferase changes. Overall, developmental BPA exposure was associated with female-predominant alterations in adipose morphology, metabolic gene expression, and lipid remodeling, with responses influenced by post-weaning diet.