In this study, we used a 1H NMR based metabolomics strategy combined with gene expression analysis to determine the combined effects of gestational exposure of mice to BPA (10 μg/kg body weight by subcutaneous injection) and arsenic (10 ppb sodium arsenite in drinking water). Results showed that exposure to either BPA or, arsenic or their combination induced age-dependent metabolic disruptions in male mice offspring, and the combined exposure could exacerbate the metabolic changes induced by either BPA or arsenic alone. Moreover, this combined exposure influenced both glucose tolerance and insulin tolerance in mice, along with changing the expression of genes involved in lipid and glucose homeostasis. Specifically, the combined exposure to BPA and arsenic promoted the uptake of glucose and fatty acid from serum to liver, and genes involved in glycogenesis, glucogenesis, and fatty acid oxidation were activated in the liver in the combined exposure group. Taken together, these experimental results highlight the importance of considering the combined toxicity of environmental pollutants at levels relevant to human exposure, especially during the early life stages of mammals.
Keywords: Arsenic; BPA; Combined effects; Glucose and lipid homeostasis; Metabolomics.
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