Increased mRNA levels of Mn-SOD and catalase in embryos of diabetic rats from a malformation-resistant strain

Previous studies have suggested that reactive oxygen species (ROS) are medi ators in the teratogenic process of diabetic pregnancy. In an animal model for diabetic pregnancy, offspring of the H rat strain show minor dysmorphog enesis when the mother is diabetic, whereas the offspring of diabetic rats of a sister strain, U, display major morphologic malformations. Earlier stu dies have shown that embryonic catalase activity is higher in the Il than i n the U strain, and maternal diabetes increases this difference in activity , The aim of this study was to characterize the influence of genetic predis position on diabetic embryopathy by comparing the mRNA levels of ROS-metabo lizing enzymes in the two strains. We determined the mRNA levels of catalas e, glutathione peroxidase, gamma-glutamylcystein-synthetase, glutathione re ductase, and superoxide dismutase (CuZn-SOD and Mn-SOD) in day 11 embryos o f normal and diabetic H and U rats using semiquantitative reverse transcrip tion-polymerase chain reaction. The mRNA levels of catalase and Mn-SOD were increased in II embryos as a response to maternal diabetes, and no differe nces were found for the other genes. Sequence analysis of the catalase prom oter indicated that the difference in mRNA levels may result from different regulation of transcription. Sequence analysis of the catalase cDNA reveal ed no differences between the two strains in the translated region, suggest ing that the previously observed difference in the electrophoretic mobility in zymograms is due to posttranslational modifications. An impaired expres sion of scavenging enzymes in response to ROS excess can thus be an integra l part of a genetic predisposition to embryonic dysmorphogenesis.