Integrated lipidomics and metabolomics approach to assess sex-dependent effects of acute bisphenol A exposure on hepatic lipid metabolism in zebrafish

High concentrations of bisphenol A (BPA), a typical endocrine disruptor, have been widely found in rivers and oceans due to its extensive use in polymer production. Direct exposure to BPA in the aquatic environment is known to have toxic effects including their immune responses, neuroendocrine and reproductive systems and development on aquatic organisms. BPA has various adverse effects associated with the lipid metabolism of fish. However, there are limited studies on the specific mechanisms on sex-dependent differences in hepatic lipid metabolism in BPA-exposed fish. Therefore, we performed comparative lipid profiling by UPLC-MS/MS and metabolite profiling by GC-MS/MS in male and female zebrafish livers during uptake and depuration of BPA. BPA exposure led to similar changes in various hepatic lipids in male and female zebrafish, but several lipids including triacylglycerols were affected differently in a sex- and exposure duration-dependent manner. There were also sex-dependent responses of hepatic metabolites such as GABA, alanine, glucose, sarcosine, and allantoin, consistent with the trends in changes in lipids in response to BPA exposure in male and female zebrafish. Overall, our study identified sex-dependent differences in specific lipids and metabolites in the liver of zebrafish exposed to BPA. These findings might provide a novel reference for understanding the metabolic toxic effects of BPA and the pathways involved in these effects in aquatic organisms.