Integrated Toxicology and Environmental Health Program, Nicholas School of the Environment, Duke University, Durham, NC, USA; Nicholas School of the Environment, Duke University, Durham, NC, USA; Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, NC, USA.
Integrated Toxicology and Environmental Health Program, Nicholas School of the Environment, Duke University, Durham, NC, USA; Nicholas School of the Environment, Duke University, Durham, NC, USA.
Sci Total Environ. 2022 Sep 10;838(Pt 4):156499. doi: 10.1016/j.scitotenv.2022.156499. Epub 2022 Jun 6.
Mixtures of per- and polyfluoroalkyl substances (PFAS) are often found in drinking water, and serum PFAS are detected in up to 99% of the population. However, very little is known about how exposure to mixtures of PFAS affects maternal and fetal health. The aim of this study was to investigate maternal, fetal, and placental outcomes after preconceptional and gestational exposure to an environmentally relevant PFAS mixture in a New Zealand White (NZW) rabbit model. Dams were exposed via drinking water to control (no detectable PFAS) or a PFAS mixture for 32 days. This mixture was formulated with PFAS to resemble levels measured in tap water from Pittsboro, NC (10 PFAS compounds; total PFAS load = 758.6 ng/L). Maternal, fetal, and placental outcomes were evaluated at necropsy. Thyroid hormones were measured in maternal serum and kit blood. Placental gene expression was evaluated by RNAseq and qPCR. PFAS exposure resulted in higher body weight (p = 0.01), liver (p = 0.01) and kidney (p = 0.01) weights, blood pressure (p = 0.05), and BUN:CRE ratio (p = 0.04) in dams, along with microscopic changes in renal cortices. Fetal weight, measures, and histopathology were unchanged, but a significant interaction between dose and sex was detected in the fetal: placental weight ratio (p = 0.036). Placental macroscopic changes were present in PFAS-exposed dams. Dam serum showed lower T4 and a higher T3:T4 ratio, although not statistically significant. RNAseq revealed that 11 of the 14 differentially expressed genes (adj. p < 0.1) are involved in placentation or pregnancy complications. In summary, exposure elicited maternal weight gain and signs of hypertension, renal injury, sex-specific changes in placental response, and differential expression of genes involved in placentation and preeclampsia. Importantly, these are the first results to show adverse maternal and placental effects of an environmentally-relevant PFAS mixture in vivo.
多氟和全氟烷基物质（PFAS）混合物经常存在于饮用水中，高达 99%的人群的血清中都能检测到 PFAS。然而，人们对接触 PFAS 混合物如何影响母婴健康知之甚少。本研究旨在新西兰白兔模型中研究孕前和孕期接触环境相关 PFAS 混合物对母婴和胎盘的影响。通过饮用水使母鼠暴露于对照（未检测到 PFAS）或 PFAS 混合物中 32 天。该混合物是根据从北卡罗来纳州皮茨堡市自来水中测量的水平（10 种 PFAS 化合物；总 PFAS 负荷 = 758.6ng/L）用 PFAS 配制的。在解剖时评估母婴和胎盘的结局。测量母血清和试剂盒血液中的甲状腺激素。通过 RNAseq 和 qPCR 评估胎盘基因表达。PFAS 暴露导致母鼠体重增加（p = 0.01）、肝脏（p = 0.01）和肾脏（p = 0.01）重量增加、血压升高（p = 0.05）和 BUN：CRE 比值升高（p = 0.04），肾脏皮质出现显微镜下变化。胎儿体重、测量值和组织病理学均未改变，但在胎儿与胎盘的重量比中检测到剂量与性别之间的显著相互作用（p = 0.036）。PFAS 暴露的母鼠出现胎盘大体变化。母鼠血清中的 T4 水平较低，T3：T4 比值较高，但无统计学意义。RNAseq 显示 14 个差异表达基因中的 11 个（adj.p<0.1）参与胎盘形成或妊娠并发症。总之，暴露引起母体体重增加和高血压、肾脏损伤、胎盘反应的性别特异性变化，以及与胎盘形成和子痫前期相关的基因的差异表达。重要的是，这些是首次在体内显示环境相关 PFAS 混合物对母婴和胎盘产生不利影响的结果。
