Effects of maternal diabetes on early embryogenesis: I. The teratogenic potential of diabetic serum

Abstract

Abstract Effects of maternal diabetes on initial stages of organogenesis was examined by culturing early somite stage mouse embryos in the presence of diabetic serum. Serum for the cultures was prepared from rats which had been made mildly or severely diabetic by the intraperitoneal administration of 50 mg/kg or 75 mg/kg streptozotocin, respectively. Effects of this diabetic serum were age‐and dose‐related, with a higher incidence of malformations occurring among younger (2–3 vs 4–6 somite) embryos and among embryos exposed to serum from severely diabetic animals. The most commonly occuring anomaly was inhibition of neural tube closure which involved cranial (exencephaly) regions only, and was accompanied by growth inhibition in embryos exposed to severely diabetic serum. Histologically, embryos cultured in diabetic serum exhibited a wave of cell necrosis which occurred during the first 4–8 h of culture and was primarily restricted to neuroepithelial and prospective neural crest cells. However, by 24 h the neurotic debris had disappeared, even in severely malformed embryos. These abnormalities are similar to central nervous system defects described for offspring from diabetic mothers. Furthermore, the severity of diabetes produced by streptozotocin treatment promoted glucose and insulin levels comparable to those observed in diabetic patients.