title: Perflurooctanoic acid induces developmental cardiotoxicity in chicken embryos and hatchlings.
abstract: Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that is detectable in serum of the general U.S. population. PFOA is a known developmental toxicant that induces mortality in mammalian embryos and is thought to induce toxicity via interaction with the peroxisome proliferator activated receptor alpha (PPARα). As the cardiovascular system is crucial for embryonic survival, PFOA-induced effects on the heart may partially explain embryonic mortality. To assess impacts of PFOA exposure on the developing heart in an avian model, we used histopathology and immunohistochemical staining for myosin to assess morphological alterations in 19-day-old chicken embryo hearts after PFOA exposure. Additionally, echocardiography and cardiac myofibril ATPase activity assays were used to assess functional alterations in 1-day-old hatchling chickens following developmental PFOA exposure. Overall thinning and thinning of a dense layer of myosin in the right ventricular wall were observed in PFOA-exposed chicken embryo hearts. Alteration of multiple cardiac structural and functional parameters, including left ventricular wall thickness, left ventricular volume, heart rate, stroke volume, and ejection fraction were detected with echocardiography in the exposed hatchling chickens. Assessment of ATPase activity indicated that the ratio of cardiac myofibril calcium-independent ATPase activity to calcium-dependent ATPase activity was not affected, which suggests that developmental PFOA exposure may not affect cardiac energetics. In summary, structural and functional characteristics of the heart appear to be developmental targets of PFOA, possibly at the level of cardiomyocytes. Additional studies will investigate mechanisms of PFOA-induced developmental cardiotoxicity.
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States.
authors.forename: Qixiao
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Lust
authors.affiliation: Human Exposure and Atmospheric Sciences Division, Methods Development and Application Branch, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709, United States.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Strynar
authors.affiliation: Human Exposure and Atmospheric Sciences Division, Methods Development and Application Branch, National Exposure Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27709, United States.
authors.forename: Sonia
authors.initials: S
authors.lastname: Dagnino
authors.affiliation: Department of Pharmacology and Toxicology, Brody School of Medicine, East Carolina University, Greenville, NC 27834, United States. Electronic address: dewittj@ecu.edu.
authors.forename: Jamie C
authors.initials: JC
authors.lastname: DeWitt
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D030161:Avian Proteins / Q000378:metabolism; D002210:Caprylates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D024722:Cardiac Myosins / Q000378:metabolism; D054715:Cardiotoxins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D002642:Chick Embryo; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004785:Environmental Pollutants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity*; D006321:Heart / Q000187:drug effects* / Q000196:embryology* / Q000503:physiopathology; D006339:Heart Rate; D006352:Heart Ventricles / Q000187:drug effects / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009210:Myofibrils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D038081:Organogenesis / Q000187:drug effects; D013318:Stroke Volume / Q000187:drug effects
chemical_list: D030161:Avian Proteins; D002210:Caprylates; D054715:Cardiotoxins; D004785:Environmental Pollutants; D005466:Fluorocarbons; D000255:Adenosine Triphosphate; C023036:perfluorooctanoic acid; D024722:Cardiac Myosins