Zinc supplementation at the time of ethanol exposure ameliorates teratogenicity in mice

BackgroundWe have previously demonstrated that ethanol teratogenicity in mice is related to the maternal expression of metallothionein (MT), a zinc (Zn)-binding protein. Ethanol induces maternal liver MT, which causes plasma Zn concentrations to decrease as Zn moves into the liver. During pregnancy it is suggested that this change decreases fetal Zn supply and contributes to abnormal development. Here we investigated whether maternal Zn supplementation at the time of ethanol exposure reduces teratogenicity.MethodsMice were injected with 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) and ZnSO4 (2.5 microg Zn/g subcutaneously at 0 hr) and were killed over 16 hr to ascertain changes in plasma Zn. Plasma Zn concentrations peaked at 2 hr, where levels were 5-fold normal and then returned toward normal over 14 hr. Pregnant mice were treated in a similar manner on gestation day 8 with saline, saline + Zn, ethanol + Zn, or ethanol alone, and fetal abnormalities were assessed on gestation day 18.ResultsExternal abnormalities were most prevalent in offspring from dams treated with ethanol. Zn treatment at the time of ethanol exposure reduced the incidence of fetal abnormalities to basal levels. Litters from dams treated with ethanol + Zn contained more fetuses and fewer fetal resorption sites compared with those from ethanol-treated dams.ConclusionsThese findings demonstrate that Zn supplementation at the time of ethanol exposure significantly negates the deleterious effects of ethanol on the fetus.Carey, Luke C. ; Coyle, Peter ; Philcox, Jeffrey C. ; Rofe, Allan M