Delayed developmental sequences in rodent diabetic embryopathy.
Diabetes induced by alloxan at day 6 of gestation in Wistar rats produced decreased fetal growth, delayed skeletal ossification, decreased fetal kidney beta-glucuronidase, and an increased frequency of fetal birth defects which correlated with the degree of diabetic control. Offspring of severely diabetic mothers (mean blood glucose greater than 501 mg/dl) sacrificed at 20 days had a mean weight of 2.12 +/- 0.16 g, a mean of 1.8 +/- 0.46 caudal ossification centers, and a 28% incidence of birth defects as compared to 3.70 +/- 0.22 g, 5.9 +/- 0.42 caudal centers, and 1.1% defects for controls. Offspring of severely diabetic mothers sacrificed at 21 days had mean numbers of caudal and sternal ossification centers which did not significantly differ from controls, indicating that decreased ossification observed at 20 days of gestation is a delayed developmental sequence which is mostly corrected by 21 days. Offspring of moderately diabetic (mean blood glucose 300-500 mg/dl) and insulin-treated dams (mean blood glucose 152-168 mg/dl) had intermediate degrees of growth or ossification delay and birth defect frequency at both the 20- and 21-day sacrifices. Maternal diabetes also retards the developmental increase in fetal kidney beta-glucuronidase such than 20-day offspring of severely diabetic mothers had a mean specific activity of 1.1 nmol/min/mg compared to 3.0 nmol/min/mg for controls. The results support prior studies in rodents suggesting a progression of early growth delay, altered developmental sequences, and birth defects in diabetic pregnancy. This progression is suggested as a common teratogenic mechanism which has implications for evaluating analogous pregnancies in man.
D000818:Animals; D000013:Congenital Abnormalities / Q000209:etiology; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000473:pathology; D005314:Embryonic and Fetal Development; D005260:Female; D005333:Fetus / Q000201:enzymology / Q000473:pathology*; D005865:Gestational Age; D007668:Kidney / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology; D008431:Maternal-Fetal Exchange; D010012:Osteogenesis; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000473:pathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012863:Skeleton / Q000473:pathology