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4090756 
Journal Article 
Antioxidative Treatment of Pregnant Diabetic Rats Diminishes Embryonic Dysmorphogenesis 
Eriksson, UJ; Cederberg, J 
2005 
Yes 
Diabetes
ISSN: 0012-1797
EISSN: 1939-327X 
DART/TER/5001560 
54 
Suppl 1 
English 
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 the 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 may further improve fetal outcome in offspring of diabetic rats, and, in addition, if such treatment may exert any adverse effects of fetal development. Non-diabetic and streptozotocin diabetic female rats were fed 2, 5, 10 or 15 % alpha-tocopherol or 4, 10 or 15 % ascorbate in their diet and fetal outcome was assessed on gestational day 20. Maternal diabetes caused increased malformation (from 0 to 29 %) and resorption (from 5 to 38 %) rates in the offspring. The malformations included micrognathia (33 %), agnathia (51 %), other facial malformation (6 %), absence of tail (7 %) or omphalocele (3 %). Both alpha-tocopherol and ascorbate treatment improved fetal morphology (to 9 and 19 % malformations, and to 9 and 26 % resorptions, respectively) in offspring of diabetic rats. There was a dose-dependent improvement for the alpha-tocopherol supplementation, where the higher doses diminished fetal dysmorphogenesis more than the 2 % diet. The ascorbate supplementation was less dose-dependant, 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 one case of agnathia in a fetus of a non-diabetic rat supplemented with 15 % alpha-tocopherol. 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 non-diabetic pregnancy.