title: Perfluorooctane sulfonate (PFOS) toxicity in domestic chicken (Gallus gallus domesticus) embryos in the absence of effects on peroxisome proliferator activated receptor alpha (PPARalpha)-regulated genes.
abstract: Perfluorooctane sulfonate (PFOS) is a widely distributed industrial compound that has been detected in the eggs of various wild avian species. Laboratory studies have indicated that PFOS is embryotoxic to domestic chickens (Gallus gallus domesticus), but the mechanisms of toxicity in the developing avian embryo remain unknown. We recently demonstrated that PFOS acts as a peroxisome proliferator by causing increased expression of peroxisome proliferator activated receptor alpha (PPARalpha)-regulated genes in cultured primary chicken embryo hepatocytes. The present study examined whether PPARalpha-regulated genes were dose-dependently affected in chicken embryos exposed in ovo to PFOS. White leghorn chicken eggs were injected with 0.1, 5.0 or 100.0 microg PFOS/g egg into the air cell prior to incubation. Embryos were incubated until pipping, after which the expression of PPARalpha-regulated genes was measured in the liver tissue of surviving embryos using real-time reverse transcription polymerase chain reaction. A dose-dependent decrease in embryo pippability was observed with an LD50 of 93 microg/g (3.54 microg/g-672,910 microg/g, 95% confidence interval). Hepatic PFOS concentrations increased concomitantly with dose. The PPARalpha-regulated genes measured were peroxisomal acyl CoA oxidase, bifunctional enzyme, liver fatty acid binding protein and peroxisomal 3-ketoacyl thiolase. PFOS exposure via egg injection prior to incubation did not affect the transcriptional activity of any of the assayed PPARalpha-regulated genes at any of the doses examined in day 21 chicken embryos.
authors.affiliation: Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jason M
authors.initials: JM
authors.lastname: O'Brien
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Carew
authors.forename: Shaogang
authors.initials: S
authors.lastname: Chu
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Letcher
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000378:metabolism; D000102:Acetyl-CoA C-Acyltransferase / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D002642:Chick Embryo / Q000187:drug effects*; D004746:Enoyl-CoA Hydratase / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D005466:Fluorocarbons / Q000633:toxicity*; D007535:Isomerases / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D047493:PPAR alpha / Q000378:metabolism*; D063994:Peroxisomal Bifunctional Enzyme; D020025:Peroxisome Proliferators / Q000633:toxicity; D020675:Peroxisomes / Q000201:enzymology
chemical_list: D017738:Alkanesulfonic Acids; D050556:Fatty Acid-Binding Proteins; D005466:Fluorocarbons; D009097:Multienzyme Complexes; D047493:PPAR alpha; D020025:Peroxisome Proliferators; C076994:perfluorooctane sulfonic acid; D010088:Oxidoreductases; D015094:3-Hydroxyacyl CoA Dehydrogenases; C107176:peroxisomal acyl-CoA oxidase; D042962:Acyl-CoA Oxidase; D000102:Acetyl-CoA C-Acyltransferase; D004746:Enoyl-CoA Hydratase; D063994:Peroxisomal Bifunctional Enzyme; D007535:Isomerases