title: Ethanol-induced fetal dysmorphogenesis in the mouse is diminished by high antioxidative capacity of the mother.
abstract: Intrauterine exposure to ethanol causes embryonic and fetal maldevelopment. Oxidative stress in mother and offspring has been suggested to be part of the teratogenic mechanism of ethanol. Here we aimed to assess the importance of maternal and fetal antioxidative capability for the risk of dysmorphogenesis in the offspring. We used male and female mice with different levels of superoxide dismutase (SOD) activity-wild-type (WT) mice, mice with a targeted SOD mutation (KO, decreased CuZnSOD mRNA), and mice transgenic for SOD (TG, increased CuZnSOD mRNA). Female WT, KO (heterozygous), and TG (heterozygous) mice were given drinking water containing 20% ethanol before and throughout gestation. Non-ethanol-exposed WT, KO, and TG mice served as controls. The female mice were mated with males with identical genotype, and the pregnancy was interrupted on gestational day 18 when the offspring was evaluated and genotyped. Fetal hepatic isoprostane (8-epi-PGF(2alpha)) levels were measured to assess the degree of fetal oxidative stress. Exposure to 20% ethanol decreased fetal weight by 9-13% in the three groups. Ethanol exposure roughly doubled the rates of maldeveloped WT and KO offspring but did not affect TG offspring. The fetal hepatic levels of 8-epi-PGF(2alpha) were increased in the ethanol-exposed WT and KO mice but not in ethanol-exposed TG mice. Ethanol exposure preferentially damaged WT fetuses in pregnant KO mice, whereas no such effect was found in the litters of ethanol-consuming TG mice. Administration of ethanol to pregnant mice disturbs embryogenesis by oxidative stress, and the adverse effects are more pronounced in offspring of mice with low antioxidative capacity.
authors.affiliation: Department of Medical Cell Biology, Biomedical Center, Uppsala Universitet, SE-751 23 Uppsala, Sweden. parri.wentzel@medcellbiol.uu.se
authors.forename: Parri
authors.initials: P
authors.lastname: Wentzel
authors.forename: Ulf J
authors.initials: UJ
authors.lastname: Eriksson
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000096:biosynthesis; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D018384:Oxidative Stress; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*
chemical_list: C075750:8-epi-prostaglandin F2alpha; D000431:Ethanol; D015237:Dinoprost; D013482:Superoxide Dismutase