title: Hepatic Mitochondrial Alteration in CD-1 Mice Associated with Prenatal Exposures to Low Doses of Perfluorooctanoic Acid (PFOA).
abstract: Perfluorooctanoic acid (PFOA) is a perfluoroalkyl acid primarily used as an industrial surfactant. It persists in the environment and has been linked to potentially toxic and/or carcinogenic effects in animals and people. As a known activator of peroxisome proliferator-activated receptors (PPARs), PFOA exposure can induce defects in fatty acid oxidation, lipid transport, and inflammation. Here, pregnant CD-1 mice were orally gavaged with 0, 0.01, 0.1, 0.3, and 1 mg/kg of PFOA from gestation days (GD) 1 through 17. On postnatal day (PND) 21, histopathologic changes in the livers of offspring included hepatocellular hypertrophy and periportal inflammation that increased in severity by PND 91 in an apparent dose-dependent response. Transmission electron microscopy (TEM) of selected liver sections from PND 91 mice revealed PFOA-induced cellular damage and mitochondrial abnormalities with no evidence of peroxisome proliferation. Within hypertrophied hepatocytes, mitochondria were not only increased in number but also exhibited altered morphologies suggestive of increased and/or uncontrolled fission and fusion reactions. These findings suggest that peroxisome proliferation is not a component of PFOA-induced hepatic toxicity in animals that are prenatally exposed to low doses of PFOA.
authors.affiliation: NTP Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Comparative Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Quist
authors.affiliation: NTP Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Filgo
authors.affiliation: UltraPath Imaging, Durham, North Carolina, USA.
authors.forename: Connie A
authors.initials: CA
authors.lastname: Cummings
authors.affiliation: Biostatistics Branch, Division of Intramural Research, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Kissling
authors.affiliation: Cellular and Molecular Pathology Branch, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Hoenerhoff
authors.affiliation: NTP Laboratory, Division of the National Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA fentonse@niehs.nih.gov.
authors.forename: Suzanne E
authors.initials: SE
authors.lastname: Fenton
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002210:Caprylates / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047493:PPAR alpha / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*
chemical_list: D002210:Caprylates; D005466:Fluorocarbons; D047493:PPAR alpha; C023036:perfluorooctanoic acid
keywords: PFOA; PPARα; hepatocellular hypertrophy; liver; mitochondrial damage; mouse; peroxisome proliferation