title: Mechanisms of selenomethionine developmental toxicity and the impacts of combined hypersaline conditions on Japanese medaka (Oryzias latipes).
abstract: Selenium (Se) is an essential micronutrient that can cause embryotoxicty at levels 7-30 times above essential concentrations. Exposure to hypersaline conditions and 50 μM selenomethionine (SeMet) decreased embryo hatch and depleted glutathione in Japanese medaka embryos without affecting Se accumulation. To better understand the impacts of nonchemical stressors on developmental toxicity of Se in fish, several adverse outcome pathways were evaluated in the Japanese medaka (Oryzias latipes). We treated medaka embryos at 12 h post fertilization with 50 μM SeMet for 12 hours in freshwater or in 13 ppth hypersalinity and evaluated the contributions of oxidative stress, the unfolded protein response and apoptosis to reduced hatch. Exposure to SeMet and hypersalinity decreased embryo hatch to 3.7% ± 1.95, and induced teratogenesis in 100% ± 0 of hatched embryos. In contrast, treatments of freshwater, saltwater, and SeMet in freshwater resulted in 89.8% ± 3.91-86.7% ± 3.87 hatch, and no significant increase in deformities. We found no significant differences in lipid peroxidation, indicating that oxidative stress may not be responsible for the observed toxicity in embryos at this time point (24 h). Although significant changes in apoptosis were not observed, we witnessed up to 100 fold increases in transcripts of the endoplasmic reticulum (ER) chaperone, immunoglobulin binding protein (BiP) and trends toward increasing downstream signals, activating transcription factor 4 (ATF4) and ATF6 indicating potential contributions of the unfolded protein response to the effects of SeMet and hypersaline conditions. These data indicate that multiple adverse outcome pathways may be responsible for the developmental toxicity of Se and salinity, and these pathways may be time dependent.
authors.affiliation: Department of Environmental Sciences, University of California- Riverside , Riverside, California 92507, United States.
authors.forename: Allison
authors.initials: A
authors.lastname: Kupsco
authors.forename: Daniel
authors.initials: D
authors.lastname: Schlenk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000187:drug effects; D029941:Fish Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects / Q000235:genetics; D009990:Oryzias / Q000196:embryology* / Q000235:genetics; D018384:Oxidative Stress / Q000187:drug effects; D054712:Salinity; D012645:Selenomethionine / Q000633:toxicity*; D018675:Toxicity Tests; D056811:Unfolded Protein Response / Q000187:drug effects / Q000235:genetics
chemical_list: D029941:Fish Proteins; D012645:Selenomethionine