Association between Prenatal Exposure to PFAS and Fetal Sex Hormones: Are the Short-Chain PFAS Safer?

Epidemiologic evidence regarding the effects of in utero exposure to per- and polyfluoroalkyl substances (PFAS), particularly short-chain PFAS, on fetal reproductive hormones is limited and inconsistent. This study aimed to assess the relationship between maternal PFAS exposure and fetal reproductive hormones. A total of 752 mother-infant pairs who were recruited in the Shanghai Birth Cohort Study between 2013 and 2016 were selected. We quantified 10 PFAS, including two short-chain PFAS congeners (perfluorobutanesulfonate, PFBS and perfluoroheptanoic acid, PFHpA), in maternal blood plasma in early pregnancy. Dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and total testosterone (TT) were measured in the umbilical cord blood using chemiluminescence kits. Free androgen index (FAI) was calculated by TT divided by SHBG. Multiple linear regression found that one ln-unit increase in maternal PFBS was associated with decreases in FSH (-0.159; 95% CI: -0.290, -0.029), LH (-0.113; 95% CI: -0.221, -0.004), and FAI (-0.009; 95% CI: -0.017, -0.001). In addition, PFHpA showed negative associations with LH (-0.154; 95% CI: -0.297, -0.011) and FAI (-0.008; 95% CI: -0.014, -0.002). When PFAS were analyzed in quartiles, significant negative associations were observed between PFBS and FSH, and between PFHpA and FAI. Overall, prenatal exposure to PFBS and PFHpA was associated with the disturbance of fetal gonadotropins as well as free androgen level in this prospective cohort, suggesting that the reproductive toxicity of short-chain PFAS may not be neglected.