Duke University School of Medicine, Durham, NC, USA.
Duke University Global Health Institute, Durham, NC, USA.
Sci Total Environ. 2024 Mar 20;917:170459. doi: 10.1016/j.scitotenv.2024.170459. Epub 2024 Jan 28.
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants ubiquitous in the environment and humans. In-utero PFAS exposure is associated with numerous adverse health impacts. However, little is known about how prenatal PFAS mixture exposure affects offspring's neurobehavioral function. This study aims to determine the causal relationship between in-utero PFAS mixture exposure and neurobehavioral changes in Sprague-Dawley rat offspring. Dams were exposed via drinking water to the vehicle (control), an environmentally relevant PFAS mixture, or a high-dose PFAS mixture. The environmentally relevant mixture was formulated to resemble measured tap water levels in Pittsboro, NC, USA (10 PFAS compounds; sum PFAS =758.6 ng/L). The high-dose PFAS load was 3.8 mg/L (5000×), within the range of exposures in the experimental literature. Exposure occurred seven days before mating until birth. Following exposure to PFAS-laden water or the vehicle during fetal development, neurobehavioral toxicity was assessed in male and female offspring with a battery of motor, cognitive, and affective function tests as juveniles, adolescents, and adults. Just before weaning, the environmentally relevant exposure group had smaller anogenital distances compared to the vehicle and high-dose groups on day 17, and males in the environmentally relevant exposure group demonstrated lower weights than the high-dose group on day 21 (p < 0.05). Reflex development delays were seen in negative geotaxis acquisition for both exposure groups compared to vehicle-exposed controls (p = 0.009). Our post-weaning behavioral measures of anxiety, depression, and memory were not found to be affected by maternal PFAS exposure. In adolescence (week five) and adulthood (week eight), the high PFAS dose significantly attenuated typical sex differences in locomotor activity. Maternal exposure to an environmentally relevant PFAS mixture produced developmental delays in the domains of pup weight, anogenital distance, and reflex acquisition for rat offspring. The high-dose PFAS exposure significantly decreased typical sex differences in locomotor activity.
全氟和多氟烷基物质（PFAS）是普遍存在于环境和人类中的持久性有机污染物。母体 PFAS 暴露与许多不良健康影响有关。然而，对于产前 PFAS 混合物暴露如何影响后代的神经行为功能知之甚少。本研究旨在确定母体 PFAS 混合物暴露与 Sprague-Dawley 大鼠后代神经行为变化之间的因果关系。通过饮用水，使母鼠暴露于载体（对照）、环境相关的 PFAS 混合物或高剂量 PFAS 混合物中。环境相关的混合物是根据美国北卡罗来纳州皮茨堡市自来水的实测水平配制的（10 种 PFAS 化合物；总 PFAS=758.6ng/L）。高剂量 PFAS 负荷为 3.8mg/L（5000 倍），处于实验文献中暴露的范围内。暴露发生在交配前七天到分娩期间。在胎儿发育过程中暴露于 PFAS 水或载体后，通过一系列运动、认知和情感功能测试，对雄性和雌性后代进行神经行为毒性评估，评估在幼年期、青少年期和成年期进行。就在断奶前，与载体组和高剂量组相比，环境相关暴露组的雄性仔鼠第 17 天的肛殖距较小，而环境相关暴露组的雄性仔鼠第 21 天的体重比高剂量组低（p<0.05）。与载体暴露对照组相比，两组暴露组的负趋地性获得均出现反射发育延迟（p=0.009）。我们在断奶后的焦虑、抑郁和记忆行为测量中没有发现母体 PFAS 暴露的影响。在青少年期（第五周）和成年期（第八周），高剂量 PFAS 显著减弱了运动活性的典型性别差异。母体暴露于环境相关的 PFAS 混合物会导致仔鼠的体重、肛殖距和反射获得方面出现发育迟缓。高剂量 PFAS 暴露显著降低了运动活性的典型性别差异。
