TERATOGENICITY OF 3-DEOXYGLUCOSONE AND DIABETIC EMBRYOPATHY

The increased rate of embryonic dysmorphogenesis in diabetic pregnancy is correlated with the severity and duration of the concurrent hyperg lycemia during early gestation. Whole embryo culture was used to inves tigate a possible association of hyperglycemia-induced disturbances of embryo development with tissue levels of the three alpha-oxoaldehydes : glyoxal, methylglyoxal, and 3-deoxyglncosone (3-DG). Rat embryos exp osed to high glucose levels in vitro showed severe dysmorphogenesis an d a 17-fold increased concentration of 3-DG compared with control embr yos cultured in a low glucose concentration. Exogenous 3-DG (100 mu mo l/l) added to the medium of control cultures yielded an increased embr yonic malformation rate and a 3-DG concentration similar to that of em bryos cultured in high glucose. Addition of superoxide dismutase (SOD) to the culture medium decreased the malformation rates of embryos exp osed to either high glucose or high 3-DG levels, but it did not decrea se the high embryonic 3-DG concentrations caused by either agent. Our results implicate the potent glycating agent 3-DG as a teratogenic fac tor in diabetic embryopathy. In addition, the anti-teratogenic effect of SOD administration appears to occur downstream of 3-DG formation, s uggesting that 3-DG accumulation leads to superoxide-mediated embryopa thy.