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.