EFFECT OF MATERNAL DIABETES AND DIETARY COPPER ON FETAL DEVELOPMENT IN RATS

To test whether diabetes associated alterations in copper metabolism c ontribute to diabetes-induced teratogenicity in rats, pregnancy outcom e was compared between diabetic and nondiabetic rats fed either a copp er adequate (12 mu g/g diet) or low copper diet (1 mu g/g diet). The d ietary regimen was begun two weeks prior to mating and continued throu ghout pregnancy. To facilitate the reduction of maternal copper stores in the low copper groups, the low copper diet was supplemented with a copper chelator, triethylenetetraamine, at 1% for one week; the chela tor was removed from the diet one week prior to mating. Pregnancy was terminated on gestation day 20. Maternal and fetal tissues were assess ed for copper concentrations, the activities of the cuproenzymes coppe r, zinc superoxide dismutase and ceruloplasmin, and the copper binding protein metallothionein. Dams fed the low copper diet had low tissue copper concentrations, and low plasma ceruloplasmin and erythrocyte su peroxide dismutase activities compared to copper-adequate dams. Fetuse s in the low copper groups were characterized by tow liver copper conc entrations. Gross structural and skeletal anomalies were only observed in the diabetic groups; maternal copper intake did not influence the frequency of these anomalies. However, fetuses in the low-copper nondi abetic group, and both diabetic groups, were characterized by low live r copper, zinc superoxide dismutase activity suggesting that fetal cop per metabolism was influenced by both copper intake and diabetes.