Untargeted metabolomic analysis of pregnant women exposure to perfluorooctanoic acid at different degrees

● Metabolome can distinguish pregnant women exposure to PFOA at different degrees. ● Metabolome can reveal the metabolic changes of pregnant women exposure to PFOA. ● PFOA exposure degrees could affect the GSH metabolism of pregnant women. ● PFOA exposure degrees could change the microbiota metabolism of pregnant women. Perfluorooctanoic acid (PFOA) is a novel type of persistent synthetic organic pollutant, and its exposure on pregnant women can cause some adverse effects, such as pregnancy-induced hypertension, gestational diabetes mellitus, and preeclampsia. Therefore, understanding the metabolic changes caused by PFOA exposure is of great significance to protect pregnant women from its adverse effects. In this study, the metabolomes from the urine samples of pregnant women exposure to PFOA at different degrees were analyzed by GC-MS and LC-MS. The samples in different groups were distinguished and the differential metabolites were screened based on the VIP value, FC, and P-value of each comparison group through multivariate statistical analysis. The pathways related to differential metabolites were searched to reveal the effects of PFOA exposure on metabolic changes in pregnant women at different degrees. Finally, the ROC of differential metabolites was performed, and the differential metabolites with large area under the curve (AUC) values were selected and compared to identify the mutually differential metabolites. Meanwhile, these metabolites were fitted with a multivariable to explore if they could be used to distinguish different groups. The quantitative comparison of mutually differential metabolites revealed that the levels of L-cysteine, glycine, and 5-aminovaleric acid were positively correlated with the degree of PFOA exposure, indicating that different degrees of PFOA exposure could affect the synthesis or degradation of GSH and change the metabolism of oral or intestinal microbiota. Additionally, they may cause oxidative stress and abnormal fat metabolism in pregnant women.