EMBRYOPATHIC EFFECTS OF THE ORAL HYPOGLYCEMIC AGENT CHLORPROPAMIDE IN CULTURED MOUSE EMBRYOS

OBJECTIVES: The oral hypoglycemic agent chlorpropamide was evaluated for embryopathic effects in the mouse embryo model. STUDY DESIGN: 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. RESULTS: Mouse embryos were malformed by greater-than-or-equal-to 24 mug/ml of chlorpropamide, embryonic protein content and somites were decreased by greater-than-or-equal-to 130 mug/ml of chlorpropamide, and visceral yolk sac protein was reduced by >500 mug/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. CONCLUSIONS: 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.