Perfluoroalkyl Substances (PFAS) and Their Effects on the Placenta, Pregnancy, and Child Development: a Potential Mechanistic Role for Placental Peroxisome Proliferator–Activated Receptors (PPARs)

• Published in: Current environmental health reports Vol. 7; no. 3; pp. 222 - 230
• Main Authors: Szilagyi, John T., Avula, Vennela, Fry, Rebecca C.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.09.2020; Springer Nature B.V
• Subjects: Adult; Biomedical and Life Sciences; Biomedicine; Child; Child Development - drug effects; Child Health; Children; Children & youth; Cohort analysis; Contaminants; Diabetes mellitus; Diabetes, Gestational - chemically induced; Disease; DNA methylation; Early Life Environmental Health (H Volk and J Buckley; Environmental Exposure - adverse effects; Environmental Health; Fatty acids; Female; Fetus - drug effects; Fetuses; Fluorocarbons - toxicity; Gestational diabetes; Glucose; Homeostasis; Human populations; Humans; Insulin; Intrauterine exposure; Lipid metabolism; Lipids; Maternal Exposure - adverse effects; Medicine/Public Health; Metabolic disorders; MicroRNAs; Molecular modelling; Nuclear receptors; Obesity; Perfluoroalkyl & polyfluoroalkyl substances; Perfluorochemicals; Peroxisome proliferator-activated receptors; Peroxisome Proliferator-Activated Receptors - metabolism; Pharmacology/Toxicology; Placenta; Placenta - drug effects; Pre-eclampsia; Pregnancy; Pregnancy complications; Pregnancy Outcome; Prenatal Exposure Delayed Effects - chemically induced; Receptors; Reviews; Section Editors; Topical Collection on Early Life Environmental Health; Toxicity; Womens health; United States > US; Pregnancy; Placenta; PPAR; Preeclampsia; Development; PFAS; In utero
• ISSN: 2196-5412; 2196-5412
• DOI: 10.1007/s40572-020-00279-0

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.