Decreased catalase activity in malformation-prone embryos of diabetic rats.
The risk for congenital malformation is increased in diabetic pregnancy. An excess of radical oxygen species (ROS) in the embryo has been suggested as a major teratogenic mechanism. We have used 2 rat strains, denoted H and U, with different catalase isoenzymes to study if the type of ROS scavenging enzyme may be of importance for the embryonic dysmorphogenesis in diabetic pregnancy. Rats were mated H x H and U x U, and about half of the females had streptozotocin-induced diabetes. Embryos were harvested from female rats on day 11 and day 20 of pregnancy. On day 11, the H embryos showed larger crown-rump length (3.9 mm) than the U embryos (2.9 mm), a difference that remained in the embryos of diabetic rats (3.1 mm and 2.5 mm in the H and U strains, respectively). H embryos displayed higher activity of catalase (1.8 +/- 0.1 U/micrograms DNA) than U embryos (1.1 +/- 0.1 U/micrograms DNA), and the difference increased further when the H and U mothers were diabetic (H: 2.1 +/- 0.2 U/micrograms DNA, U: 0.6 +/- 0.1 U/micrograms DNA). In the day-20 fetuses, diabetes in the mother caused increased resorption rate in both strains (from 3.2% to 10.6% in H rats, from 6.8% to 39.5% in U rats), and high rate of congenital malformations in the U strain (H: 0% malformations, U: 20% malformations). We found a strain-related difference in embryo catalase activity with higher activity in the teratogenically resistant H embryos compared to the malformation-prone U embryos. Provided that this difference between the strains signifies a genetic difference of functional antioxidative importance, the results may suggest that catalase enzyme activity has a protective role in opposing embryonic dysmorphogenesis in diabetic rat pregnancy.
Cederberg
J
J
Department of Medical Cell Biology, University of Uppsala, Sweden. joce@hem.passagen.se
Eriksson
U J
UJ
D000014:Abnormalities, Drug-Induced / Q000201:enzymology*; D000818:Animals; D002374:Catalase / Q000378:metabolism*; D004247:DNA / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D010064:Embryo Implantation; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000737:chemistry / Q000201:enzymology*; D005260:Female; D005327:Fetal Resorption; D007527:Isoenzymes / Q000378:metabolism*; D008098:Litter Size; D011247:Pregnancy; D051381:Rats; D013045:Species Specificity
D007527:Isoenzymes; D004247:DNA; D002374:Catalase