Prevention of diabetes-associated embryopathy by overexpression of the free radical scavenger copper zinc superoxide dismutase in transgenic mouse embryos.
OBJECTIVE
It has recently been suggested that oxygen free radicals are involved in the high incidence of fetal dysmorphogenesis that is associated with diabetic pregnancies. The purpose of the current investigation was to study the effect of copper zinc superoxide dismutase, a free radical scavenging enzyme, on the prevention of diabetes-associated embryopathy in mice.


METHODS
Mice used in this study were either transgenic, bearing the human copper zinc superoxide dismutase gene, or nontransgenic controls. Diabetes was generated by streptozotocin administration on days 6 and 7 of gestation. Hyperglycemia developed on day 8 and was maintained through day 10 (critical period of organogenesis). On day 10 fetuses were examined for external anomalies, and their crown-rump lengths and deoxyribonucleic acid content were determined.


RESULTS
Induction of maternal diabetes produced a significant reduction in mean crown-rump length of control embryos (4.48 +/- 0.7 mm vs 3.65 +/- 0.6 mm, p = 0.0001), whereas transgenic embryos were not affected (4.72 +/- 0.6 mm vs 4.45 +/- 0.8 mm, p > 0.05). After induction of diabetes fetal loss and malformation rates were significantly higher in control embryos (6.0% vs 23.8% and 8.4% vs 16.5%, respectively). Transgenic embryos were practically unaffected by diabetes and showed fetal loss and malformation rates of 5.9% and 4.4%, respectively, after induction of diabetes.


CONCLUSIONS
Elevated levels of copper zinc superoxide dismutase, a key enzyme in the metabolism of free oxygen radicals, elicit a protective effect against diabetes-associated embryopathy.
D000704:Analysis of Variance; D000818:Animals; D016009:Chi-Square Distribution; D000013:Congenital Abnormalities / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004622:Embryo, Mammalian / Q000201:enzymology; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D016017:Odds Ratio; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D016166:Free Radical Scavengers; D013482:Superoxide Dismutase