Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic rats

Abstract

Although improved metabolic control of maternal diabetes has reduced the rate of complications during pregnancy, the incidence of congenital malformations is still increased in children of insulin-dependent-diabetic (IDDM) mothers [1±4]. The mechanisms by which maternal diabetes disrupts embryonic development are not completely understood, but the risk of fetal malformation is strongly correlated to the maternal glucose concentration [2±4]. Maternal levels of triglycerides, b-hydroxybutyrate and branched chain amino acids are also of importance for the occurrence of fetal dysmorphogenesis [5]. In the embryo, disturbed metabolism of sorbitol, inositol, arachidonic acid and prostaglandins has been demonstrated in experimental diabetic pregnancy and Diabetologia (1997 Vitamin C supplementation of the maternal diet reduces the rate of malformation in the offspring of diabetic ratsDepartment of Medical Cell Biology, Uppsala University, Uppsala, SwedenSummary An excess of reactive oxygen species (ROS) has been associated with the increased rate of congenital malformations in experimental diabetic pregnancy. Previous in vitro and in vivo studies show that antioxidants can protect the embryonic development in a diabetic environment. In the present investigation we examined the antiteratogenic capacity of vitamin C, an antioxidative agent not previously evaluated as a dietary supplement in diabetic pregnancy. Normal and streptozotocin diabetic rats were either fed a standard diet or a diet enriched with 0.9, 1.8 or 4 % sodium ascorbate throughout pregnancy. On gestational day 20, the litters of normal and diabetic rats without vitamin C supplement contained 9 and 12 % early resorptions, 2 and 17 % late resorptions and 1 and 27 % malformations, respectively. Vitamin C treatment reduced the rates of late resorptions and malformations in the diabetic groups in proportion to the dose administered. Thus, in the diabetic group with 4 % ascorbate treatment we found unchanged numbers of early resorptions, but only 7 % late resorptions (p < 0.05 vs untreated diabetic pregnancy) and 8 % malformations (p < 0.05 vs untreated diabetic pregnancy). Maternal diabetes did not alter tissue levels of ascorbic acid in the fetuses at term, whereas vitamin C treatment caused accumulation of ascorbic acid in the placenta, maternal and fetal liver. Vitamin C supplementation yielded increased a-tocopherol concentration in the placenta and caused a reduction of the high concentrations of thiobarbituric acid reactive substances (TBARS) in serum of pregnant diabetic rats. Vitamin C treatment reduces the rates of congenital malformations and late resorptions, thereby supporting that ROS are involved in the embryonic dysmorphogenesis of diabetic pregnancy. [Diabetologia (1997 Keywords Diabetic pregnancy, streptozotocin, rat, embryo, fetus, congenital malformation, vitamin C, antioxidant therapy, TBARS, oxidative stress. Corresponding author: C. M. Sima  n, Department of Medical Cell Biology, Uppsala University, Biomedicum, P. O. Box 571, S-751 23 Up...

Oxidant regulation of gene expression and neural tube development: Insights gained from diabetic pregnancy on molecular causes of neural tube defects

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Transgenic mice overproducing human thioredoxin-1, an antioxidative and anti-apoptotic protein, prevents diabetic embryopathy

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Reduction in diabetes‐induced craniofacial defects by maternal immune stimulation

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