Effects on the liver lipidome of rat offspring prenatally exposed to bisphenol A

Abstract Bisphenol A (BPA) is a well-known endocrine disruptor that has obesogenic properties. We have previously reported changes in hepatic transcriptome and proteome of several lipid homeostasis-related genes in a sex-dependent manner in rat offspring prenatally exposed to BPA. To further understand the impacts of prenatal BPA exposure, we analyzed lipidomic profiles in the postnatal day (PND) 21 and 60 rats using a high-resolution QTOF mass spectrometer coupled with a HPLC system. We found that the total lipid content was significantly decreased in PND21 females prenatally exposed to 5000 μg/kg bw/day of BPA. Levels of total fatty acids, acylcarnitines, and monoacylglycerols significantly increased in both female and male BPA-exposed rats at PND21. An elevation in total cholesterol esters and reductions in triacylglycerols and monogalactosyl diacyglycerols were found only in PND21 females prenatally exposed to BPA. Interestingly, opposite responses were observed for phospholipids and sphingolipids between PND21 females and males following BPA exposure. The effects on the body weight and total lipid content were mitigated in the latter stage, although the alterations of lipid profiles continued until PND60. A Data Integration Analysis for Biomarker discovery using Latent cOmponents (DIABLO) revealed a high correlation of the lipidome with our previously published transcriptome data. DIABLO also identified potential biomarkers of prenatal exposure to BPA; glycerol-3-phosphate dehydrogenase 1 (Gpd1) and glyceronephosphate O-acyltransferase (Gnpat), which are involved in the glycerophospholipid metabolism, in females and males, respectively. Collectively, we highlighted the sex- and age-dependent effects of prenatal BPA exposure on hepatic lipid homeostasis in rat offspring.