1H NMR-based serum metabolomics analysis of the age-related metabolic effects of perinatal exposure to BPA, BPS, BPF, and BPAF in female mice offspring

The widespread application of bisphenols (BPs) in the industry has made them ubiquitous in the environment, causing potential environmental risks. Its unknown impacts on human being have received more and more attention. In this study, we have assessed the metabolic effects of perinatal exposure to bisphenol A (BPA) and its substitutes (bisphenol S (BPS), bisphenol F (BPF), and bisphenol AF (BPAF)) in female mice adolescent offspring and female mice adulthood offspring. H-1 NMR-based serum metabolomics showed that metabolic profiles were disturbed with BPA and its three substitutes exposure in female mice adolescent offspring and female mice adulthood offspring. In addition, age-related metabolic effects were found based on changes in serum endogenous metabolites and metabolic pathways. Specifically, metabolic pathway analysis showed that major disturbed metabolic pathways in female mice adulthood offspring compare with female mice adolescent offspring also changed significantly. With the increase of age of the female mice offspring, changes in the metabolic pathways became more obvious in the BPA treatment group. Conversely, partially disturbed metabolic pathways were restored in the BPS, BPF, and BPAF treatment groups. In conclusion, perinatal exposure to BPA and its three substitutes significantly interferes with metabolic profiles and metabolic pathways, and this metabolic effects were age-related. These results offer more detailed information about the age-related metabolic effects of perinatal exposure to BPA, BPS, BPF, and BPAF in female mice offspring and provide data for systematic evaluation of the health risk assessment of BPA and its substitutes.