Skeletal growth of fetuses from streptozotocin diabetic rat mothers: in vivo and in vitro studies

Abstract

For largely unknown reasons severe or moderate diabetes of pregnant rats results in pronounced fetal growth retardation. Therefore, some skeletal growth parameters of fetal rats from streptozotocin diabetic mothers were studied in vivo and in vitro. Two days post conception rats were intravenously injected with 65 mg/kg body weight streptozotocin. On day 20 post conception 8 normal and 8 diabetic rat mothers received 5 mu Ci 3-H thymidine intraperitoneally. One day later the experiments were terminated. Fetal body weight and body length were significantly (p less than 0.05-0.001) reduced in the hyperglycaemic rats compared to normal rats, as was the thymidine incorporation into rib cartilage (p less than 0.02). In the cell culture colony formation from isolated chondrocytes of normal and hyperglycaemic fetuses was determined. Proinsulin, insulin (62.5-250 ng/ml), insulin-like growth factor I and II (6.25-25 ng/ml) significantly (p less than 0.05-0.001) augmented colony formation in a dose-dependent manner, with the somatomedins being 8 times more effective than proinsulin or insulin. Isolated chondrocytes from hyperglycaemic compared to normal fetuses formed significantly (p less than 0.05-0.001) fewer colonies in the basal state and in response to all 4 hormones. The results confirm the growth retardation of fetuses from diabetic rat mothers. A reduced responsiveness of chondrocytes from hyperglycaemic fetuses to various growth factors could be demonstrated as compared to cells from normal fetuses.