Transcriptomics integrated with metabolomics reveals perfluorobutane sulfonate (PFBS) exposure effect during pregnancy and lactation on lipid metabolism in rat offspring

Emerging epidemiological evidence indicates potential associations between gestational perfluorobutane sulfonate (PFBS) exposure and adverse metabolic outcomes in offspring. However, the underlying mechanisms remain unclear. Our study aimed to investigate PFBS exposure effects during pregnancy and lactation on rat offspring lipid profiles and the possible underlying mechanisms. Although the biochemical index difference including total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine amino transaminase (ALT), aspartate amino transferase (AST), and fasting blood glucose between exposed groups and the control group was not significant, transcriptome analyses showed that the differentially expressed genes (DEGs) in the 50 mg/kg/day PFBS exposure group were significantly related to protein digestion and absorption, peroxisome proliferator activated-receptor (PPAR) signaling pathway, xenobiotic metabolism by cytochrome P450, glycine, serine and threonine metabolism, β-alanine metabolism, bile secretion, unsaturated fatty acid (FA) biosynthesis, and alanine, aspartate and glutamate metabolism. Untargeted metabolomics analyses identified 17 differential metabolites in the 50 mg/kg/day PFBS exposure group. Among these, phosphatidylserine [PS (18:0/22:6(4Z,7Z,10Z,13Z,16Z,19Z))], lysoPE (18:1(11Z)/0:0), and PS (14:0/20:4(5Z,8Z,11Z,14Z)) were significantly correlated with phospholipid metabolism disorders. Correlation analysis indicated the DEGs, including FA binding protein (Fabp4), spermine oxidase (Smox), Fabp2, acyl-CoA thioesterase 5 (Acot5), sarcosine dehydrogenase (Sardh), and amine oxidase, copper-containing 3 (Aoc3) that significantly enriched in xenobiotic metabolism by cytochrome P450 and glycine, serine, and threonine metabolism signaling pathways were highly related to the differential metabolite pantetheine 4'-phosphate. Pantetheine 4'-phosphate was significantly negatively associated with non-high-density lipoprotein (non-HDL) and TC levels. Collectively, our study indicated that maternal PFBS exposure at a relatively low level could alter gene expression and metabolic molecules in lipid metabolism-related pathway series in rat offspring, although the effects on metabolic phenotypes were not significant within the limited observational period, using group-wise and trend analyses.