title: Disruption of circulation by ethanol promotes fetal alcohol spectrum disorder (FASD) in medaka (Oryzias latipes) embryogenesis.
abstract: Japanese medaka (Oryzias latipes) embryos exposed to ethanol have developed craniofacial, cardiovascular and skeletal defects which can be compared with the phenotypic features of fetal alcohol spectrum disorder (FASD) observed in human. The present experiment was designed to show that the disruption in circulation by ethanol during embryogenesis is a potential cause of FASD. Fertilized eggs were exposed to ethanol (0, 100 and/or 400 mM) for 24 or 48 h at various developmental stages (Iwamatsu stages 4-30) and were analyzed at 6 day post fertilization (dpf). It was observed that controls and the embryos exposed to 100 mM ethanol were in circulating state; however, a significant number of embryos of stages 4-24 exposed to 400 mM ethanol had disrupted circulation. Compared to controls, protein and RNA contents were significantly reduced in non-circulating embryos. Lipid peroxidation (LPO) analysis was made at 3, 6, 24, 48, 96 and 144 hour post fertilization (hpf). LPO was increased with the advancement of morphogenesis; however, ethanol or the circulation status had no effect. We further analyzed alcohol dehydrogenase (Adh 5 and adh8) and aldehyde dehydrogenase (Aldh9A and Aldh1A2) enzyme mRNAs in the embryos exposed to 400 mM ethanol for 24 h. A developmental stage-specific reduction in these enzyme mRNAs by ethanol was observed. We conclude that ethanol-induced disruption in circulation during embryogenesis is a potential cause of the development of FASD features in medaka.
authors.affiliation: National Center for Natural Product Research, Environmental Toxicology Research Program, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, MS 38677, USA.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Hu
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Asok K
authors.initials: AK
authors.lastname: Dasmahapatra
mesh_terms: D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000098:blood supply / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology*; D015227:Lipid Peroxidation / Q000187:drug effects; D009990:Oryzias / Q000196:embryology*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D000431:Ethanol; C475662:alcohol dehydrogenase 8; D000426:Alcohol Dehydrogenase; D000445:Aldehyde Oxidoreductases; D000444:Aldehyde Dehydrogenase; C087006:formaldehyde dehydrogenase, glutathione-independent