Reduced SOD activity and increased neural tube defects in embryos of the sensitive but not of the resistant Cohen diabetic rats cultured under diabetic conditions.
BACKGROUND
The role of reactive oxygen species in the etiology of diabetes-induced anomalies was studied in a genetic model of nutritionally induced Type 2 diabetes mellitus: the Cohen diabetic sensitive (CDs) and resistant (CDr) rats. We have previously shown in this model that embryopathy may be induced by a combination of genetic and environmental factors. In our study we investigated the role of the antioxidant defense mechanism, genetic predisposition or environmental factors in embryos cultured under diabetic conditions.


METHODS
CDs, CDr and Sabra rat 11.5-day old embryos were studied after 28 hr of culture in control (low glucose), high glucose, diabetic sub-teratogenic, and diabetic teratogenic media. Embryos were monitored for growth retardation and congenital anomalies. Activity of superoxide dismutase (SOD) and catalase-like (CAT) enzymes was measured in embryonic homogenates.


RESULTS
In control medium, CDs embryos were significantly underdeveloped but exhibited no anomalies and SOD activity was not significantly different from that of CDr embryos. In high glucose medium, CDs embryos were smaller than CDr and Sabra embryos and smaller than CDs embryos cultured in control medium. Neural tube defects (NTD) were found predominantly in the CDs embryos starting from 14% in the high glucose medium and increasing to 29% in the sub-teratogenic medium. In the teratogenic medium, < 50% of the CDs and Sabra embryos were alive whereas all (100%) of the CDr embryos were alive. SOD activity significantly increased in CDs embryos when cultured in the high glucose medium but was significantly reduced in the sub-teratogenic medium. SOD activity was increased significantly in the Sabra embryos cultured in the sub-teratogenic medium but did not change in CDr embryos cultured in either one of the different culture media. CAT activity did not show any significant trend in either one of the rat strains or in any of the different culture conditions.


CONCLUSIONS
Our results suggest that genetic susceptibility plays an important role in inducing underdevelopment and NTD in cultured CDs embryos in sub-teratogenic medium and in protecting the CDr embryos under the same conditions. The combination of a sub-teratogenic environment with genetic susceptibility is sufficient to reduce the activity of SOD, hence decreasing the ability of the CDs embryos to cope with diabetic sub-teratogenic environment and prevent NTD.
Weksler-Zangen
Sarah
S
Laboratory of Teratology, Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Yaffe
Pirhiya
P
Ornoy
Asher
A
D020155:3-Hydroxybutyric Acid / Q000494:pharmacology; D000090:Acetoacetates / Q000494:pharmacology; D000818:Animals; D002374:Catalase / Q000096:biosynthesis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D020964:Embryo Loss; D004622:Embryo, Mammalian / Q000187:drug effects / Q000201:enzymology*; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D020022:Genetic Predisposition to Disease; D005947:Glucose / Q000494:pharmacology; D009436:Neural Tube Defects / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D009924:Organ Culture Techniques; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000096:biosynthesis*
D000090:Acetoacetates; D004338:Drug Combinations; C016635:acetoacetic acid; D002374:Catalase; D013482:Superoxide Dismutase; D005947:Glucose; D020155:3-Hydroxybutyric Acid