{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T17:35:34Z","timestamp":1760204134506},"reference-count":55,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2006,2,8]],"date-time":"2006-02-08T00:00:00Z","timestamp":1139356800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>We have previously shown that oxidative stress is important in the pathogenesis of diabetes\u2010induced anomalies in Cohen Diabetic sensitive (CDs) rat embryos and seems to interplay with genetic factors. We investigated the role of genetic factors related to the antioxidant defense mechanism in CDs rat embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We studied 11.5\u2010 and 12.5\u2010day embryos of Cohen Diabetic resistant (CDr) and CDs rats that were fed a regular diet (RD), and hence not diabetic, compared to rats fed a high\u2010sucrose low\u2010copper diet (HSD) where only the CDs animals became diabetic. Embryos were monitored for growth and congenital anomalies. mRNA of catalase (CAT), glutathione peroxidase (GSHpx), CuZn\u2010SOD (SOD\u2010superoxide dismutase), and Mn\u2010SOD and the extent of nuclear factor kappa B (NF\u2010\u03baB) activation were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Embryos of CDs dams fed RD were significantly smaller and had an increased rate of NTDs compared to embryos of CDr dams fed RD. When CDs dams were fed HSD, &gt;50% of the CDs embryos were dead and 44% of the live embryos had NTDs. Live 11.5\u2010day old embryos of CDs dams fed RD had a statistically significant increase in CAT, CuZn\u2010SOD, and GSHpx mRNA levels compared with the levels in the CDr embryos from dams fed RD. CDs embryos from dams fed HSD showed significant overactivation of NF\u2010\u03baB compared with CDr embryos from dams fed HSD (in which activation was decreased), without any increase in the expression of SOD, CAT, and GSHpx.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This study demonstrates that one of the genetic differences between the CDr and CDs strains fed RD is an increased expression of genes encoding for antioxidant enzymes in the CDs but inability for upregulation in diabetes. In addition, while activation of NF\u2010\u03baB is decreased in CDr on HSD, it is increased in the CDs. These differences may play a role in the increased sensitivity of the CDs embryos to diabetic\u2010induced teratogenicity. 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