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 elevated glucose levels in diabetic embryopathy.


METHODS
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.
Reece
E A
EA
Department of Obstetrics, Gynecology and Reproductive Sciences, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Wiznitzer
A
A
Homko
C J
CJ
Hagay
Z
Z
Wu
Y K
YK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D000013:Congenital Abnormalities / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000150:complications*; D005260:Female; D006330:Heart Defects, Congenital / Q000209:etiology; D009436:Neural Tube Defects / Q000209:etiology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose