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.

中文翻译：

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产前暴露于PFAS与胎儿性激素之间的关联：短链PFAS是否更安全？

关于宫内暴露于全氟和多氟烷基物质（PFAS），特别是短链PFAS对胎儿生殖激素的影响的流行病学证据有限且不一致。这项研究旨在评估母体PFAS暴露与胎儿生殖激素之间的关系。选择了2013年至2016年间在上海出生队列研究中招募的752对母婴。我们对孕早期孕妇血浆中的10种PFAS进行了定量，包括两个短链PFAS同系物（全氟丁烷磺酸盐，PFBS和全氟庚酸，PFHpA）。使用化学发光试剂盒测定了脐带血中的硫酸脱氢表雄酮硫酸盐（DHEA-S），性激素结合球蛋白（SHBG），促黄体生成激素（LH），促卵泡激素（FSH）和总睾丸激素（TT）。通过TT除以SHBG计算游离雄激素指数（FAI）。多元线性回归分析发现，孕妇PFBS升高1 ln单位与FSH（-0.159; 95％CI：-0.290，-0.029），LH（-0.113; 95％CI：-0.221，-0.004）有关，和FAI（-0.009； 95％CI：-0.017，-0.001）。此外，PFHpA与LH（-0.154; 95％CI：-0.297，-0.011）和FAI（-0.008; 95％CI：-0.014，-0.002）呈负相关。当在四分位数中分析PFAS时，在PFBS和FSH之间以及PFHpA和FAI之间观察到显着的负关联。总体而言，在该前瞻性队列研究中，产前暴露于PFBS和PFHpA与胎儿促性腺激素的紊乱以及游离雄激素水平有关，这表明短链PFAS的生殖毒性可能不会被忽略。