title: Developmental toxicity of perfluorooctane sulfonate (PFOS) is not dependent on expression of peroxisome proliferator activated receptor-alpha (PPAR alpha) in the mouse.
abstract: Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are members of a family of perfluorinated compounds. Both are environmentally persistent and found in the serum of wildlife and humans. PFOS and PFOA are developmentally toxic in laboratory rodents. Exposure to these chemicals in utero delays development and reduces postnatal survival and growth. Exposure to PFOS on the last 4 days of gestation in the rat is sufficient to reduce neonatal survival. PFOS and PFOA are weak agonists of peroxisome proliferator activated receptor-alpha (PPAR alpha). The reduced postnatal survival of neonatal mice exposed to PFOA was recently shown to depend on expression of PPAR alpha. This study used PPAR alpha knockout (KO) and 129S1/SvlmJ wild type (WT) mice to determine if PPAR alpha expression is required for the developmental toxicity of PFOS. After mating overnight, the next day was designated gestation day (GD) 0. WT females were weighed and dosed orally from GD15 to 18 with 0.5% Tween-20, 4.5, 6.5, 8.5, or 10.5mg PFOS/kg/day. KO females were dosed with 0.5% Tween-20, 8.5 or 10.5mg PFOS/kg/day. Dams and pups were observed daily and pups were weighed on postnatal day (PND) 1 and PND15. Eye opening was recorded from PND12 to 15. Dams and pups were killed on PND15, body and liver weights recorded, and serum collected. PFOS did not affect maternal weight gain or body or liver weights of the dams on PND15. Neonatal survival (PND1-15) was significantly reduced by PFOS in both WT and KO litters at all doses. WT and KO pup birth weight and weight gain from PND1 to 15 were not significantly affected by PFOS exposure. Relative liver weight of WT and KO pups was significantly increased by the 10.5mg/kg dose. Eye opening of PFOS-exposed pups was slightly delayed in WT and KO on PND13 or 14, respectively. Because results in WT and KO were comparable, it is concluded that PFOS-induced neonatal lethality and delayed eye opening are not dependent on activation of PPAR alpha.
authors.affiliation: Reproductive Toxicology Division, 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: Reproductive Toxicology Division, 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: Cynthia J
authors.initials: CJ
authors.lastname: Wolf
authors.affiliation: Reproductive Toxicology Division, 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: Reproductive Toxicology Division, 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: Robert D
authors.initials: RD
authors.lastname: Zehr
authors.affiliation: Reproductive Toxicology Division, 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: Judith E
authors.initials: JE
authors.lastname: Schmid
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Lindstrom
authors.affiliation: Human Exposure and Atmospheric Sciences Division, National Exposure Research Laboratory, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, NC 27711, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.affiliation: Reproductive Toxicology Division, 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: D017738:Alkanesulfonic Acids / Q000819:agonists / Q000633:toxicity*; D000818:Animals; D001724:Birth Weight; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000819:agonists / Q000633:toxicity*; D005123:Eye / Q000187:drug effects / Q000254:growth & development; D005260:Female; D005466:Fluorocarbons / Q000819:agonists / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000254:growth & development; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D047493:PPAR alpha / Q000378:metabolism*; D012737:Sex Factors; D016019:Survival Analysis
chemical_list: D017738:Alkanesulfonic Acids; D004785:Environmental Pollutants; D005466:Fluorocarbons; D047493:PPAR alpha; C076994:perfluorooctane sulfonic acid