Antioxidative treatment of pregnant diabetic rats diminishes embryonic dysmorphogenesis

BACKGROUND: Diabetic pregnancy is still associated with an increased rate of congenital malformations despite extensive clinical efforts to normalize the risk for the offspring. The etiology of diabetic embryopathy is not clear; however, experimental studies have suggested a role for oxidative stress in the teratogenicity of diabetic pregnancy. The antioxidants alpha-tocopherol and ascorbate have improved fetal outcome in diabetic rodent pregnancy when supplemented in moderate to high doses. In the present work we investigated if extremely high doses of either alpha-tocopherol or ascorbate might further improve fetal outcome in offspring of diabetic rats and, in addition, if such treatment may exert any adverse effects of fetal development. METHODS: Nondiabetic and streptozotocin diabetic female rats were fed 2, 5, 10, or 15% a-tocopherol or 4, 10, or 15% ascorbate in their diet. RESULTS: Both alpha-tocopherol and ascorbate treatment improved fetal morphology in offspring of diabetic rats. There was a dose-dependent improvement for the alpha-tocopherol supplementation, in which the higher doses diminished fetal dysmorphogenesis more than the 2% diet. The ascorbate supplementation was less dose-dependent; however, the higher doses tended to improve fetal outcome more than the lower doses. No adverse effects of the antioxidants were noted in the offspring with the exception of 1 case of agnathia in a fetus of a nondiabetic rat supplemented with 15% alpha-tocopherol. CONCLUSIONS: These results indicate that very high doses of dietary antioxidants may be needed to normalize the development of the offspring in experimental diabetic pregnancy, but that treatment with such high doses may also have adverse effects in nondiabetic pregnancy.