SYNCHRONIZATION OF THE FACTORS CRITICAL FOR DIABETIC TERATOGENESIS - AN IN-VITRO MODEL

OBJECTIVE: Our goal was to determine the relationship between critical factors and conditions such as gestational age and exposure time to e levated glucose levels in diabetic embryopathy. STUDY DESIGN: A postim plantation rat embryo culture was used as a model for investigation. T he effect of various factors on embryonic development was studied. Exp eriments were conducted with increasing glucose concentrations (150 to 905 mg/dl, n=186), at various gestational ages (10 to 12 days, n=169) , and for varying durations of exposure (30 to 180 minutes, n=169). Gr oss morphologic characteristics of the yolk sac and embryo were assess ed. RESULTS: Embryopathy was induced by hyperglycemia in a dose-relate d fashion: a 20% rate at two times control glucose concentration, almo st a 50% rate at four times control, and approximately a 100% abnormal ity rate at more than six times control. A critical window in gestatio nal age, days 10 to 11, and a minimum exposure time to hyperglycemia o f 2 hours were necessary to induce teratogenesis. CONCLUSIONS: Diabeti c teratogenesis occurs in a dose-related fashion and requires a minimu m exposure time and critical gestational age. Only synchronization of these critical conditions induces embryonic maldevelopment. Furthermor e, nonsynchronized aberrant conditions may result in apparently normal embryonic development.