title: Tris(1,3-dichloro-2-propyl) phosphate perturbs the expression of genes involved in immune response and lipid and steroid metabolism in chicken embryos.
abstract: We previously demonstrated that in ovo exposure to the flame retardant tris(1,3-dichloro-2-propyl) phosphate (TDCPP) decreased plasma thyroxine levels, reduced growth parameters, and decreased gallbladder size in chicken embryos. In the current study DNA microarrays were used to evaluate global mRNA expression in liver tissue of male chicken embryos that exhibited the above mentioned effects. Injected doses were dimethyl sulfoxide vehicle control, 7.6 or 45 μg TDCPP/g egg. TDCPP caused significant changes in the expression of five genes at the low dose and 47 genes at the high dose (False Discovery Rate p ≤ 0.1, fold change ≥ 1.5). The gene expression analysis suggested a compromised immune function, a state of cholestatic liver/biliary fibrosis, and disrupted lipid and steroid metabolism. Circulating bile acid levels were elevated, which is an indication of liver dysfunction, and plasma cholesterol levels were reduced; however, hepatic bile acid and cholesterol levels were unaltered. Interactome analyses identified apolipoprotein E, hepatocyte nuclear factor 4 alpha, and peroxisome proliferator-activated receptor alpha as key regulatory molecules involved in the effects of TDCPP. Our results demonstrate a targeted effect of TDCPP toxicity on lipid metabolism, including cholesterol, that helps explain the aforementioned phenotypic effects, as chicken embryos are highly dependent on yolk lipids for growth and maintenance throughout development. Finally, our results are in concordance with the literature that describes TDCPP as a cancer-causing agent, since the majority of dysregulated genes were involved in cancer pathways.
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada; National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Amani
authors.initials: A
authors.lastname: Farhat
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.
authors.forename: Julie K
authors.initials: JK
authors.lastname: Buick
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, ON K1A 0K9, Canada.
authors.forename: Jason M
authors.initials: JM
authors.lastname: O'Brien
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Doug
authors.initials: D
authors.lastname: Crump
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Kim L
authors.initials: KL
authors.lastname: Williams
authors.affiliation: National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chiu
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, ON K1N 6N5, Canada; National Wildlife Research Centre, Environment Canada, Ottawa, ON K1A 0H3, Canada. Electronic address: sean.kennedy@ec.gc.ca.
authors.forename: Sean W
authors.initials: SW
authors.lastname: Kennedy
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001647:Bile Acids and Salts / Q000097:blood; D002642:Chick Embryo; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism; D007107:Immune System / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009943:Organophosphorus Compounds / Q000633:toxicity*; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*; D013974:Thyroxine / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D001647:Bile Acids and Salts; D051557:Hepatocyte Nuclear Factor 4; D009943:Organophosphorus Compounds; D047493:PPAR alpha; D012333:RNA, Messenger; D013256:Steroids; D002784:Cholesterol; C016805:tris(1,3-dichloro-2-propyl)phosphate; D013974:Thyroxine
keywords: Chicken; Lipid metabolism; Organophosphate flame retardant; Steroid metabolism; Tris(1,3-dichloro-2-propyl) phosphate; mRNA expression microarray