title: Effects of perfluorooctanoic acid (PFOA) on expression of peroxisome proliferator-activated receptors (PPAR) and nuclear receptor-regulated genes in fetal and postnatal CD-1 mouse tissues.
abstract: PPARs regulate metabolism and can be activated by environmental contaminants such as perfluorooctanoic acid (PFOA). PFOA induces neonatal mortality, developmental delay, and growth deficits in mice. Studies in genetically altered mice showed that PPARα is required for PFOA-induced developmental toxicity. In this study, pregnant CD-1 mice were dosed orally from GD1 to 17 with water or 5mg PFOA/kg to examine PPARα, PPARβ, and PPARγ expression and profile the effects of PFOA on PPAR-regulated genes. Prenatal and postnatal liver, heart, adrenal, kidney, intestine, stomach, lung, spleen, and thymus were collected at various developmental ages. RNA and protein were examined using qPCR and Western blot analysis. PPAR expression varied with age in all tissues, and in liver PPARα and PPARγ expression correlated with nutritional changes as the pups matured. As early as GD14, PFOA affected expression of genes involved in lipid and glucose homeostatic control. The metabolic disruption produced by PFOA may contribute to poor postnatal survival and persistent weight deficits of CD-1 mouse neonates.
authors.affiliation: Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States. Electronic address: Abbott.barbara@epa.gov.
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Abbott
authors.affiliation: Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Wood
authors.affiliation: Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Watkins
authors.affiliation: Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Katoria
authors.initials: K
authors.lastname: Tatum-Gibbs
authors.affiliation: Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Kaberi P
authors.initials: KP
authors.lastname: Das
authors.affiliation: Developmental Toxicology Branch, Toxicity Assessment Division (MD-67), National Health and Environmental Effects Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lau
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002210:Caprylates / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D004785:Environmental Pollutants / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000235:genetics; D005466:Fluorocarbons / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D005865:Gestational Age; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009928:Organ Specificity; D047492:Peroxisome Proliferator-Activated Receptors / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D047492:Peroxisome Proliferator-Activated Receptors; C023036:perfluorooctanoic acid