Association between Perfluorooctanoic Acid–Related Poor Embryo Quality and Metabolite Alterations in Human Follicular Fluid during IVF: A Cohort Study
Junting Xu, Qiaoling Wang, Xianting Jiao, Pengcheng Kong, Siyu Chen, Wanli Yang, Wenqiang Liu, Kunming Li, Xiaoming Teng, Yi Guo
Abstract
BACKGROUND: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been shown to disrupt normal follicular development and ovulation. However, it is unknown which specific PFAS in follicular fluid negatively impact oocyte development and embryo quality or whether any of the metabolites present in the follicular fluid contribute to these adverse effects. OBJECTIVES: We conducted a cross-sectional and cohort study to identify specific PFAS with significant adverse effects on embryo quality and their associated modes of action. METHODS: We enrolled 378 women undergoing assisted reproductive technology (ART) and collected follicular fluid samples during oocyte retrieval. We performed PFAS detection and untargeted metabolomics on the follicular fluid. The associations of individual PFAS with high-quality embryo rates and clinical pregnancy outcomes were assessed using beta regression and logistic regression, respectively, and the potential joint effect of mixtures of PFAS was assessed using Bayesian kernel machine regression (BKMR) and quantile g-computation models. A causal mediation effect model was performed to estimate the average indirect impact of PFAS, mediated by high-quality embryo rates, on clinical pregnancy outcomes, as well as its direct impact representing all other causal effects. Spearman's rank correlation coefficient was used to identify the associations between the differentially expressed metabolites and the high-quality embryo rates. RESULTS: -lauroyl-d-erythro-sphinganine) in the follicular fluid were associated with PFOA-related poor embryo quality. CONCLUSIONS: High exposure to follicular fluid PFAS was negatively correlated with embryo quality during ART, with PFOA likely to be the major contributor. PFOA-related poor embryo quality was associated with the reduction of organonitrogens and sphingolipids metabolites that are crucial for the maintenance of normal cell growth and metabolism. https://doi.org/10.1289/EHP15422.