Fetal Brain Development in Diabetic Guinea Pigs

Abstract

SummaryFetal brain development was investigated near term in guinea pigs rendered diabetic with streptozotocin. The liver and the placenta were used as reference organs. Compared to controls, those fetuses from diabetic animals had normal cerebrum and cerebellum weights, but higher liver and placenta weights in relation to fetal weights. Although liver and placenta cell number (DNA content) was unchanged, it was significantly increased in the fetal cerebrum and cerebellum of diabetics. Although the tissue protein concentration was decreased in the liver and the placenta, it was unchanged and even increased in the cerebrum and cerebellum, respectively. The concentration of myelin (cerebroside-sulfatide) was unchanged in the cerebrum, but it was increased in the cerebellum of diabetic animals.These data suggest that diabetes has a growth-promoting effect on the fetal brain cell number. Furthermore, differences in the protein content between fetal organs may reflect abnormalities in protein metabolism which do not affect the brain during diabetic pregnancies.Textbooks of pediatrics and neonatology have repeatedly reported low brain weights in relation to body weights in macrosomic babies of diabetic mothers (2, 1 1, 24, 27). Gruenwald (1 4) has reported that the rate of growth of human fetal brain is diminished in diabetic pregnancies past 30 weeks of gestation. Decreased fetal brain weight in diabetic pregnancies has also been reported by Driscoll et ul. (10) suggesting that maternal diabetes may interfere with fetal brain development.In a recent study, a decreased placental transfer of amino acids to the fetus was found in diabetic guinea pigs (22). Consequently, diabetic pregnancy has been proposed as a new model of fetal malnutrition (23). While it has been shown that those parameters such as brain weight, cell number, protein content, and myelination were affected in situations of fetal malnutrition (3,6,12,29,30) these characteristics of fetal brain development have not been investigated in diabetic pregnancies.The goal of this study was to investigate fetal brain development during diabetic pregnancies, with regard to cerebral and cerebellar DNA, protein content, and myelination (cerebrosidesulfatide content). In order to detect any specific effects of diabetes on brain development, other organs such as the liver and placenta were also examined. The guinea pig was selected as the model in view of its brain maturity at birth which approaches the human situation more than other species (1,5,8,9).Female guinea pigs of the Hartley strain were fed a standard diet (guinea pig chow, Ralston Purina), with free access to water, and were maintained under normal laboratory conditions. Because insulin-induced hypoglycemia potentiates the diabetogenic activity of streptozotocin in this species (4,15,20), the animals were given streptozotocin (1 50 mg/kg) IV (diabetic animals) or an equivalent amount of a saline solution (control animals) 90 min after one IV injection of 15 units of crystalline insulin.After mating, day 1...

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