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.