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Interactive effects of alcohol and diabetes during pregnancy on the rat fetus Lin, Yi


Substantial literature indicates that maternal diabetes has teratogenic effects on the fetus and that consumption of alcohol during gestation is also teratogenic to the fetus. In the present study, Sprague-Dawley female rats were used to test whether small amounts of alcohol administered during organogenesis has an effect on the outcome of pregnancy in nondiabetic rats; to confirm the teratogenic effect of diabetes on fetuses; and to establish whether there is an interaction between alcohol and diabetes on the outcome of pregnancy. All rats were fed Purina rat chow and tap water ad libitum. Diabetes was induced by tail vein administration of streptozotocin (60 mg/kg body weight) one week before mating. Alcohol was administered during organogenesis (days 6-11 of gestation) intragastrically. The incidence and types of external and skeletal malformations were recorded in the fetuses of all treatment groups on day 21 of gestation. In addition, the fetal development was followed by assessing the ossification of the skeleton on gestational day 21 with the aid of alizarin red S and alcian blue 8GS staining. The results of this investigation support the view of previous studies that maternal diabetes is teratogenic to the offspring in terms of significantly increased malformation rates, and retarded fetal development (smaller fetal weight, bigger placenta, and retarded skeletal ossification compared to controls). Consumption of a small amount of alcohol (2g/kg/day) during organogenesis (days 6-11 of gestation) did not seem to intoxicate the dams, the body weight gain was at a normal rate, and there was a bigger fetal/placental ratio compared to controls. In terms of skeletal development, alcohol exposure seemed to enhance bone development. However, there were a few fetuses with absence of ossification centers in the hyoid bone and the short 13th rib which were significantly different from other treatment groups. Whether this represents retarded skeletal development is not clear. In the present study, a significant interaction between maternal diabetes and alcohol administration during organogenesis was observed. The fetal external malformation rate was significantly increased in diabetic rats exposed to alcohol compared to diabetic rats not exposed to alcohol. Furthermore, more fetuses had poorly ossified thoracic vertebral centers, poorly ossified cervical arches, and poorly ossified supraoccipital bone in diabetic rats exposed to alcohol than in diabetic rats not exposed to alcohol. These observations suggest that a small amount of alcohol consumption during organogenesis could possibly exacerbate the embryotoxic effects of maternal diabetes.

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