Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats

作者：Justin M. Conley, Christy Lambright, Nicola Evans, Mark J. Strynar, James McCord, Barry Mcintyre, Gregory S. Travlos, Mary C. Cardon, Elizabeth Medlock-Kakaley, Phillip C. Hartig, Vickie S. Wilson, L. Earl Gray · 发表于：Environmental Health Perspectives · 年份：2019 · DOI：10.1289/ehp4372 · 被引用次数：172 · 研究领域：Per- and polyfluoroalkyl substances research、Effects and risks of endocrine disrupting chemicals、Toxic Organic Pollutants Impact

BACKGROUND: Hexafluoropropylene oxide dimer acid [(HFPO-DA), GenX] is a member of the per- and polyfluoroalkyl substances (PFAS) chemical class, and elevated levels of HFPO-DA have been detected in surface water, air, and treated drinking water in the United States and Europe. OBJECTIVES: We aimed to characterize the potential maternal and postnatal toxicities of oral HFPO-DA in rats during sexual differentiation. Given that some PFAS activate peroxisome proliferator-activated receptors (PPARs), we sought to assess whether HFPO-DA affects androgen-dependent development or interferes with estrogen, androgen, or glucocorticoid receptor activity. METHODS: Steroid receptor activity was assessed with a suite of in vitro transactivation assays, and Sprague-Dawley rats were used to assess maternal, fetal, and postnatal effects of HFPO-DA exposure. Dams were dosed daily via oral gavage during male reproductive development (gestation days 14-18). We evaluated fetal testes, maternal and fetal livers, maternal serum clinical chemistry, and reproductive development of F1 animals. RESULTS: HFPO-DA exposure resulted in negligible in vitro receptor activity and did not impact testosterone production or expression of genes key to male reproductive development in the fetal testis; however, in vivo exposure during gestation resulted in higher maternal liver weights ([Formula: see text]), lower maternal serum thyroid hormone and lipid profiles ([Formula: see text]), and up-regulated gene expres...