Increased Incidence of Congenital Malformations in the Offspring of Diabetic Rats and Their Prevention by Maternal Insulin Therapy
Increased Incidence of Congenital Malformations in the Offspring of Diabetic Rats and Their Prevention by Maternal Insulin Therapy
复制标题
糖尿病大鼠后代先天性畸形发生率增加及其母体胰岛素治疗的预防
DOI：
10.2337/diab.31.1.1
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发表时间：
1982
期刊：
影响因子：
7.7
通讯作者：
C. Hellerström
中科院分区：
文献类型：
--
作者：
U. Eriksson;E. Dahlström;K. Larsson;C. Hellerström
Intensive care of the pregnant mother with diabetes has dramatically decreased the incidence of diabetic fetopathy. The persistently high rate of fetal and neonatal mortality in diabetic pregnancies is nowadays mainly due to the increased incidence of serious congenital malformations. However, attempts to elucidate the precise teratogenic mechanisms have been sparse, presumably because of a lack of relevant animal models. In the present study we recorded the incidence and types of skeletal malformations in live offspring of normal rats and in rats made diabetic with the B-cytotoxic agent streptozotocin (SZ) at least 2 wk before conception. In some of the diabetic animals insulin treatment was begun 1 wk after the SZ injection and continued throughout pregnancy. In addition, the fetal development was followed by assessing the calcification of the skeleton on gestational days 20 and 22 with the aid of Alazarin Red S staining. Manifest diabetes in the pregnant rat induced a decrease in fetal weight and viability and marked retardation of skeletal maturation. In addition, about 20% of 135 viable fetuses showed skeletal malformations comprising either micrognathia or caudal dysgenesis. These defects were not found in 314 offspring of the control rats. Only two cases of caudal dysgenesis and none of micrognathia were detected among 233 offspring of the insulin-treated rats. The present data underscore the importance of a strict differentiation in the offspring of the diabetic rat between transient development retardations and true malformations. They also demonstrate that correction of the maternal glucose intolerance is crucial for preventing the fetus from developing skeletal malformations. Altogether the data suggest that fetal malformations in the diabetic rat are attributable either to the hyperglycemia as such or to some accompanying metabolic consequence of insulin deficiency.
