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 hyperglycemia during early gestation. Whole embryo culture was used to investigate a possible association of hyperglycemia-induced disturbances of embryo development with tissue levels of the three alpha-oxoaldehydes: glyoxal, methylglyoxal, and 3-deoxyglucosone (3-DG). Rat embryos exposed to high glucose levels in vitro showed severe dysmorphogenesis and a 17-fold increased concentration of 3-DG compared with control embryos cultured in a low glucose concentration. Exogenous 3-DG (100 micromol/l) added to the medium of control cultures yielded an increased embryonic malformation rate and a 3-DG concentration similar to that of embryos cultured in high glucose. Addition of superoxide dismutase (SOD) to the culture medium decreased the malformation rates of embryos exposed to either high glucose or high 3-DG levels, but it did not decrease the high embryonic 3-DG concentrations caused by either agent. Our results implicate the potent glycating agent 3-DG as a teratogenic factor in diabetic embryopathy. In addition, the anti-teratogenic effect of SOD administration appears to occur downstream of 3-DG formation, suggesting that 3-DG accumulation leads to superoxide-mediated embryopathy.
Eriksson
U J
UJ
Department of Medical Cell Biology, University of Uppsala, Sweden. ulf.eriksson@medcellbiol.uu.se
Wentzel
P
P
Minhas
H S
HS
Thornalley
P J
PJ
D000818:Animals; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000196:embryology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology; D006037:Glyoxal / Q000378:metabolism; D006943:Hyperglycemia / Q000503:physiopathology; D008297:Male; D011247:Pregnancy; D011765:Pyruvaldehyde / Q000378:metabolism; D051381:Rats; D013723:Teratogens / Q000633:toxicity*
D013723:Teratogens; D006037:Glyoxal; D011765:Pyruvaldehyde; D003847:Deoxyglucose; C016350:3-deoxyglucosone; D005947:Glucose