Embryopathic effects of the oral hypoglycemic agent chlorpropamide in cultured mouse embryos.

Abstract

The oral hypoglycemic agent chlorpropamide was evaluated for embryopathic effects in the mouse embryo model. Mouse embryos (n = 10 to 31 per group) were exposed in whole embryo culture to serum from chlorpropamide-treated rats or chlorpropamide-supplemented control rat serum. Hypoglycemic serum from chlorpropamide-treated rats was supplemented with glucose to control for effects of hypoglycemia. Differences in malformation rates were evaluated by Fisher's exact test and numerical differences by analysis of variance. Mouse embryos were malformed by > or = 24 micrograms/ml of chlorpropamide, embryonic protein content and somites were decreased by > or = 130 micrograms/ml of chlorpropamide, and visceral yolk sac protein was reduced by > 500 micrograms/ml of chlorpropamide. Similar development occurred in serum from chlorpropamide-treated rats and chlorpropamide-supplemented control serum, and growth was not improved by adding glucose. Chlorpropamide produces malformations and growth retardation in mouse embryos in vitro at concentrations overlapping therapeutic levels in humans. Chlorpropamide-induced defects are not mediated by hypoglycemia or by products of chlorpropamide metabolism.