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 α-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) 40: 1416–1424]
Keywords Diabetic pregnancy - streptozotocin - rat - embryo - fetus - congenital malformation - vitamin C - antioxidant therapy - TBARS - oxidative stress.
Received: 15 April 1997 and in revised form: 12 August 1997