Gundacker Claudia, Audouze Karine, Widhalm Raimund, Granitzer Sebastian, Forsthuber Martin, Jornod Florence, Wielsøe Maria, Long Manhai, Halldórsson Thórhallur Ingi, Uhl Maria, Bonefeld-Jørgensen Eva Cecilie
Institute of Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria.
Unit T3S, Université Paris Cité, Inserm U1124, 75006 Paris, France.
Toxics. 2022 Nov 12;10(11):684. doi: 10.3390/toxics10110684.
Prenatal exposure to per- and polyfluorinated substances (PFAS) may impair fetal growth. Our knowledge of the underlying mechanisms is incomplete. We used the Adverse Outcome Pathway (AOP)-helpFinder tool to search for studies published until March 2021 that examined PFAS exposure in relation to birth weight, oxidative stress, hormones/hormone receptors, or growth signaling pathways. Of these 1880 articles, 106 experimental studies remained after abstract screening. One clear finding is that PFAS are associated with oxidative stress in in vivo animal studies and in vitro studies. It appears that PFAS-induced reactive-oxygen species (ROS) generation triggers increased peroxisome proliferator-activated receptor (PPAR)γ expression and activation of growth signaling pathways, leading to hyperdifferentiation of pre-adipocytes. Fewer proliferating pre-adipocytes result in lower adipose tissue weight and in this way may reduce birth weight. PFAS may also impair fetal growth through endocrine effects. Estrogenic effects have been noted in in vivo and in vitro studies. Overall, data suggest thyroid-damaging effects of PFAS affecting thyroid hormones, thyroid hormone gene expression, and histology that are associated in animal studies with decreased body and organ weight. The effects of PFAS on the complex relationships between oxidative stress, endocrine system function, adipogenesis, and fetal growth should be further explored.
产前暴露于全氟和多氟烷基物质（PFAS）可能会损害胎儿生长。我们对其潜在机制的了解并不完整。我们使用不良结局途径（AOP）-帮助查找工具搜索截至2021年3月发表的研究，这些研究考察了PFAS暴露与出生体重、氧化应激、激素/激素受体或生长信号通路之间的关系。在这1880篇文章中，经过摘要筛选后剩下106项实验研究。一个明确的发现是，在体内动物研究和体外研究中，PFAS与氧化应激有关。似乎PFAS诱导的活性氧（ROS）生成会触发过氧化物酶体增殖物激活受体（PPAR）γ表达增加以及生长信号通路的激活，导致前脂肪细胞过度分化。增殖的前脂肪细胞减少会导致脂肪组织重量降低，进而可能降低出生体重。PFAS还可能通过内分泌效应损害胎儿生长。在体内和体外研究中均已观察到雌激素效应。总体而言，数据表明PFAS对甲状腺有损害作用，影响甲状腺激素、甲状腺激素基因表达和组织学，在动物研究中这些与体重和器官重量降低有关。PFAS对氧化应激、内分泌系统功能、脂肪生成和胎儿生长之间复杂关系的影响应进一步探究。
