Effects of maternal diabetes on early embryogenesis: II. Hyperglycemia‐induced exencephaly

Abstract

Abstract Teratogenic effects of hyperglycemia on early stages of embryogenesis were investigated using the whole embryo culture technique. Young (0–1 and 2–3 somites) and old (4–6 somites) mouse embryos were exposed for 24 h to diabetic levels of excess glucose equal to 5× and 8× the normal blood glucose levels. A high frequency of neural tube defects (exencephaly) was observed in embryos maintained at either concentration, and this effect was dose‐ and age‐dependent. Thus, younger embryos (0–3 somites) were more frequently affected than older ones, and more embryos were affected at the higher dose than the lower one. Although malformations were observed, amounts of total protein were similar between control and treated cultures except for the youngest (0–1 somite) embryos, which had significantly lower amounts of protein than controls. Histological analysis of embryos maintained in 8× glucose for 4, 8, and 24 h after initiation of culture showed only a slight amount of pyknotic debris in the neuroepithelium and revealed no other causes for the abnormality. Inhibition of neural tube closure observed in this study is similar to that occasionally described in infants of diabetic mothers, and suggests that hyperglycemia may play a role in production of the malformation.