Altered Levels of Scavenging Enzymes in Embryos Subjected to a Diabetic Environment

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Abstract
Maternal diabetes during pregnancy is associated with an increased rate of congenital malformations in the offspring. The exact molecular etiology of the disturbed embryogenesis is unknown, but an involvement of radical oxygen species in the teratological process has been suggested. Oxidative damage presupposes an imbalance between the activity of the free oxygen radicals and the antioxidant defence mechanisms on the cellular level. The aim of the present study was to investigate if maternal diabetes in vivo, or high glucose in vitro alters the expression of the free oxygen radical scavenging enzymes superoxide dismutase (CuZnSOD and MnSOD), catalase and glutathione peroxidase in rat embryos during late organogenesis. We studied offspring of normal and diabetic rats on gestational days 11 and 12, and also evaluated day-11 embryos after a 48 hour culture period in 10 m M or 50 mM glucose concentration. Both maternal diabetes and high glucose culture caused growth retardation and increased rate of congenital malformations in the embryos. The CuZnSOD and MnSOD enzymes were expressed on gestational day 11 and both CuZnSOD, MnSOD and catalase were expressed on day 12 with increased concentrations of MnSOD transcripts when challenged by a diabetic milieu. There was a good correlation between mRNA, protein, and activity levels, suggesting that the regulation of these enzymes occurs primarily at the pre-translational level. Maternal diabetes in vivo and high glucose concentration in vitro induced increased MnSOD expression, concomitant with increased total SOD activity, and a tentative decrease in catalase expression and activity in the embryos. These findings support the notion of enhanced oxidative stress in the embryo as an etiologic agent in diabetic teratogenesis.