Early‐Life Exposure to Bisphenol A Damaged Pancreas That May Increase Offspring Sensitivity to High‐Fat Diets

Previous studies have identified early life as a sensitive window for BPA exposure that may increase the risk of metabolic disease in adulthood. However, less attention has been paid to the effects of early-life BPA exposure on the pancreas and its relationship to the development of metabolic diseases. In this study, we exposed females to 50 μg/kg/d BPA in drinking water from 6 days of gestation to weaning of offspring mice and administered a high-fat diet after weaning of offspring mice. We found that early-life BPA-exposed male mice gained body weight, had downregulated pancreatic <i>Ins1</i>, <i>Pdx1</i>, and <i>NeuroG3</i> gene expression, reduced β-cell mass, and resulted in abnormalities in glucose tolerance and insulin tolerance, whereas no significant alterations were observed in females. Lipidomic analyses of mouse pancreas using high-resolution mass spectrometry showed that early-life BPA exposure significantly altered the pancreas of offspring males. Lipid profiles of mouse pancreatic ceramidase gene mRNA expression were upregulated, enzyme activity was enhanced, and pancreatic ceramides, especially long-chain ceramides, were increased in abundance, the latter of which was closely correlated with the increased pancreatic MDA content as well as the decreased SOD enzyme activity. Taken together, our results suggest that early-life BPA exposure may increase the susceptibility of mice to a high-fat diet by altering pancreatic lipid metabolism in mice and that there are significant sex differences in this effect.