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Synchronization of the factors critical for diabetic teratogenesis: an in vitro model
E A Reece1, A Wiznitzer, C J Homko
1Department of Obstetrics, Gynecology and Reproductive Sciences, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Objective:
Our goal was to determine the relationship between critical factors and conditions such as gestational age and exposure time to elevated glucose levels in diabetic embryopathy.
Study Design:
A postimplantation rat embryo culture was used as a model for investigation. The effect of various factors on embryonic development was studied. Experiments 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). Gross morphologic characteristics of the yolk sac and embryo were assessed.
Results:
Embryopathy was induced by hyperglycemia in a dose-related fashion: a 20% rate at two times control glucose concentration, almost a 50% rate at four times control, and approximately a 100% abnormality rate at more than six times control. A critical window in gestational age, days 10 to 11, and a minimum exposure time to hyperglycemia of 2 hours were necessary to induce teratogenesis.
Conclusions:
Diabetic teratogenesis occurs in a dose-related fashion and requires a minimum exposure time and critical gestational age. Only synchronization of these critical conditions induces embryonic maldevelopment. Furthermore, nonsynchronized aberrant conditions may result in apparently normal embryonic development.