The Role of Reactive Oxygen Species in Diabetes-Induced Anomalies in Embryos of Cohen Diabetic Rats

The role of the antioxidant defense mechanism in diabetesinducedanomalies was studied in the Cohen diabetes-sensitive(CDs) and -resistant (CDr) rats, a genetic model of nutritionallyinduced type 2 diabetes mellitus. Embryos, 12.5-day-old, of CDsand CDr rats fed regular diet (RD) or a diabetogenic high-sucrosediet (HSD) were monitored for growth retardation and congenitalanomalies. Activity of superoxide dismutase (SOD) and catalaselikeenzymes and levels of ascorbic acid (AA), uric acid (UA), anddehydroascorbic acid (DHAA) were measured in embryonic homogenates.When fed RD, CDs rats had a decreased rate of pregnancy,and an increased embryonic resorption. CDs embryos weresmaller than CDr embryos; 46% were maldeveloped and 7% exhibitedneural tube defects (NTDs). When fed HSD, rate of pregnancywas reduced, resorption rate was greatly increased (56%;P < .001), 47.6% of the embryos were retrieved without heartbeats, and 27% exhibited NTD. In contrast, all the CDr embryoswere normal when fed RD or HSD. Activity of SOD and catalasewas not different in embryos of CDs and CDr rats fedRD. When fedHSD, levels of AA were significantly reduced, the ratio DHAA/AAwas significantly increased, and SOD activity was not sufficientlyincreased when compared to embryos of CDr. The reduced fertilityof the CDs rats, the growth retardation, and NTD seem to begenetically determined. Maternal hyperglycemia seems to result in environmentally induced embryonic oxidative stress, resulting infurther embryonic damage.