Effects of in vivo exposure of pregnant hamsters to glucose. 1. Abnormalities in LVG strain fetuses following intermittent multiple treatments with two isomers

Abstract

The increased frequency of congenital malformations including caudal regression syndrome, in infants of women with insulin-dependent diabetes mellitus is well documented. Most of the related animal research has involved the in vitro embryo culturing methodology. This study involved the alternative in vivo approach in order to determine the effects of treatment of pregnant hamsters with the D- and L-isomers of glucose at five times just before and during the period of embryonic organogenesis on maternal blood glucose levels and the rates and types of fetal abnormalities. One group of animals was injected with 5 doses (4 g/kg each) of D-glucose, i.e., on gestation day (D) 6, 3 PM; D7, 8 AM and 3 PM; D8, 8 AM and 3 PM. Two other groups were treated the same way but with L-glucose (4 g/kg per dose) and water (10 ml/kg per dose), respectively. The D-glucose treatment produced alternating periods of hyperglycemia and normoglycemia in the pregnant hamsters, enlarged placentae and fetuses with small urinary bladders, microphthalmia and skeletal abnormalities of the sternum, caudal vertebrae, pelvic bones, and femora. The L-glucose treatment did not produce changes in maternal blood D-glucose levels but did produce fetuses with small urinary bladders, microphthalmia and abnormal ossification limited to the manubrium. Several interpretations of the D-glucose-induced fetal abnormalities involving the vertebrae, proximal hindlimb bones and urinary bladders are discussed, including the consideration that this cluster has interesting similarities to the spectrum of skeletal and soft tissue abnormalities of human diabetes-related caudal regression syndrome.