title: Embryo Microinjection of Selenomethionine Reduces Hatchability and Modifies Oxidant Responsive Gene Expression in Zebrafish.
abstract: In previous studies we demonstrated that exposure to selenomethionine (SeMet) causes developmental toxicities in zebrafish (Danio rerio). The objectives of this study were to establish a dose-response relationship for developmental toxicities in zebrafish after embryo microinjection of Se (8, 16 or 32 μg/g dry mass of eggs) in the form of SeMet, and to investigate potential underlying mechanism(s) of SeMet-induced developmental toxicities. A dose-dependent increase in frequencies of mortality and total deformities, and reduced hatchability were observed in zebrafish exposed to excess Se via embryo microinjection. The egg Se concentration causing 20% mortality was then used to investigate transcript abundance of proteins involved in antioxidant protection and methylation. Excess Se exposure modified gene expression of oxidant-responsive transcription factors (nuclear factor erythroid 2-related factor nrf2a and nrf2b), and enzymes involved in cellular methylation (methionine adenosyltransferase mat1a and mat2ab) in zebrafish larvae. Notably, excess Se exposure up-regulated transcript abundance of aryl hydrocarbon receptor 2 (ahr2), a signalling pathway involved in the toxicity of dioxin-related compounds. Our findings suggest that oxidative stress or modification of methylation, or a combination of these mechanisms, might be responsible for Se-induced developmental toxicities in fishes.
authors.affiliation: Toxicology Graduate Program, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5B3.
authors.forename: J K
authors.initials: JK
authors.lastname: Thomas
authors.affiliation: Toxicology Centre, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5B3.|Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada S7N 5B4.
authors.forename: D M
authors.initials: DM
authors.lastname: Janz
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D051268:GA-Binding Protein Transcription Factor / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008845:Microinjections; D051267:NF-E2-Related Factor 2; D018384:Oxidative Stress; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics; D012644:Selenium Radioisotopes / Q000008:administration & dosage / Q000633:toxicity*; D012645:Selenomethionine / Q000008:administration & dosage / Q000633:toxicity*; D064793:Teratogenesis; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics; D029961:Zebrafish Proteins / Q000235:genetics*
chemical_list: C474372:AHR2 protein, zebrafish; D051268:GA-Binding Protein Transcription Factor; D051267:NF-E2-Related Factor 2; D018336:Receptors, Aryl Hydrocarbon; D012644:Selenium Radioisotopes; D029961:Zebrafish Proteins; C495638:nfe2l2a protein, zebrafish; D012645:Selenomethionine