Perfluoroalkyl Substances (PFAS) and Their Effects on the Placenta, Pregnancy, and Child Development: a Potential Mechan
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EARLY LIFE ENVIRONMENTAL HEALTH (H VOLK AND J BUCKLEY, SECTION EDITORS)
Perfluoroalkyl Substances (PFAS) and Their Effects on the Placenta, Pregnancy, and Child Development: a Potential Mechanistic Role for Placental Peroxisome Proliferator–Activated Receptors (PPARs) John T. Szilagyi 1,2 & Vennela Avula 1,3 & Rebecca C. Fry 1,2,3
# Springer Nature Switzerland AG 2020
Abstract Purpose of Review This review summarizes studies highlighting perfluoroalkyl substances (PFAS) and their effects on the placenta, pregnancy outcomes, and child health. It highlights human population-based associations as well as in vitro-based experimental data to inform an understanding of the molecular mechanisms underlying these health effects. Among the mechanisms by which PFAS may induce toxicity is via their interaction with the peroxisome proliferator-activated receptors (PPARs), nuclear receptors that regulate lipid metabolism and placental functions important to healthy pregnancies, as well as fetal and child development. Recent Findings In utero exposure to prevalent environmental contaminants such as PFAS is associated with negative health outcomes during pregnancy, birth outcomes, and later in life. Specifically, PFAS have been associated with increased incidence of gestational diabetes, childhood obesity, preeclampsia, and fetal growth restriction. In terms of placental molecular mechanisms underlying these associations, studies demonstrate that PFAS interfere with trophoblast lipid homeostasis, inflammation, and invasion. Moreover these effects could be mediated in part by the interaction between PFAS and PPARs, as well as other biological mechanisms. Summary This review summarizes how PFAS, critical environmental contaminants, may contribute to diseases of pregnancy as well as early and later child health. Keywords PPAR . Placenta . PFAS . Preeclampsia . In utero . Pregnancy . Development
Introduction The placenta is a temporary organ that connects the fetus with the maternal blood supply through the endometrium. The primary function of the placenta is to ensure that the fetus This article is part of the Topical Collection on Early Life Environmental Health * Rebecca C. Fry [email protected] 1
Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
2
Curriculum in Toxicology and Environmental Medicine, University of North Carolina, Chapel Hill, NC, USA
3
Institute for Environmental Health Solutions, University of North Carolina, Chapel Hill, NC, USA
develops properly throughout pregnancy [1]. To accomplish this, the placenta performs endocrine, immune, and chemical exchange functions that maintain optimal conditions for fetal development [1]. The placenta regulates the flow of nutrients in and waste out of the fetal compartment, thereby meeting the high metabolic demand of the developing fetus [2]. Because of its role in fetal development, disturbances to placental homeostasis, such as those induced by exposure to chemical subst
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