Effects of hyperglycemia and ketone bodies on the in vitro development of early somite rate embryos.

The teratogenic effects of diabetes are attributed to the influence of hyperglycemia and hyperketonemia as well as to other metabolic factors. We studied the effects of ketone bodies and glucose on the development of early somite rat embryos (day 10 1/2 of gestation) cultured in vitro. D-glucose was added to normal rat serum in concentrations of 2, 5, and 10 mg/ml. Ketone bodies (acetoacetate and beta-hydroxybutyrate, B-HOB) were individually added to normal or to hyperglycemic sera (total glucose concentrations of 3 mg/ml) in the following concentrations: acetoacetate--5, 10, 20, and 40 micrograms/ml; B-HOB--2, 5, and 8 mg/ml. The higher concentrations of each of the substances induced growth retardation and abnormalities. The growth-retarding and teratogenic effects of a combination of the substances, glucose and B-HOB, glucose and acetoacetate, on the development of 10 1/2 day embryos were greater than when each substance was added separately, even at relatively low doses. The greatest teratogenic effects were observed when low concentrations of all three substances were added simultaneously to the culture medium. These results may have direct relevance to human diabetes since diabetes is characterized by a simultaneous elevation of serum levels of all these substances.