AScribe Newswire , Joslin Diabetes Center, March 26, 2003
Joslin Study Shows How Antioxidants May Be Critical to Preventing Birth Defects in Babies of Women With Diabetes; Research Focused on Neural Tube Defects
BOSTON, March 26 (AScribe Newswire) -- One day, doctors may advise pregnant women who have diabetes to eat lots of spinach, swiss chard, wheat germ and other foods high in antioxidants as a way to reduce the risk of neural tube defects in their unborn babies. Scientists at Joslin Diabetes Center working with mice report on-line today and in the April issue of Diabetologia that oxidative stress disrupts the expression of specific genes in the embryo, and may be a more common cause of birth defects in the babies of women with and without diabetes than is currently appreciated.
Even with good control of diabetes, the risk for neural tube and other birth defects among women with diabetes is two to five times higher than those without diabetes. The most common neural tube defect in humans is spina bifida (a condition in which the spinal cord is not completely enclosed).
"Neural tube defects occur very early in pregnancy, about the time a woman may realize that she is pregnant," said the lead author of the study, Mary Loeken, Ph.D., a researcher at Joslin and Assistant Professor of Medicine (Physiology) at Harvard Medical School. "Therefore, if further studies show that antioxidants can prevent neural tube defects in the babies of diabetic mothers, antioxidant supplementation of the diets of women with diabetes during childbearing years may have the same public health benefit as folic acid supplementation for all women of childbearing years."
For more than 10 years, Loeken has studied how diabetic pregnancy affects genes in the embryo. Recently, she has focused on the role of the Pax-3 gene. Her lab found that embryos of diabetic mouse mothers have low levels of Pax-3 gene expression, and develop neural tube defects three times more often than do those of nondiabetic mice. Mouse embryos that lack functional Pax-3 genes are always born with neural tube defects, showing that normal expression of Pax-3 is absolutely required for neural tube development.
Loeken's lab has previously shown that when the mouse mother's glucose (blood sugar) levels are abnormally high, as occurs with both type 1 and type 2 diabetes, and can sometimes occur if the mother is obese, the glucose levels in the embryo are high. The high glucose levels lead to reduced expression of Pax-3 and neural tube defects.
It is known that when too much glucose is taken up by cells, including embryo cells, free radicals are increased. If free radicals are produced faster than they can be eliminated by antioxidants, oxidative stress occurs. Since the free radical eliminating system of the embryo is immature, it may be particularly vulnerable to oxidative stress. This latest study tested the hypothesis that oxidative stress inhibits expression of Pax-3, which would provide a molecular basis for neural tube defects induced by diabetic pregnancy.
"Oxidative stress has conventionally been thought to damage cells by causing DNA breakdown and cell death, but the surprising observation from this study was that even mild oxidative stress, which is insufficient to directly cause cell death, can cause birth defects by disturbing embryonic gene expression," Loeken said. "Oxidative stress can also result from ionizing radiation and certain drugs, so mild oxidative stress, sufficient to disturb expression of critical embryonic genes, could explain some birth defects during nondiabetic pregnancy. In addition, folic acid deficiency can lead to accumulation of homocysteine, which causes oxidative stress. This may explain why folic acid supplementation can prevent neural tube defects in some babies."
The research, supported by grants from the American Diabetes Association and the National Institutes of Health, was conducted by members of the Loeken laboratory at Joslin, as well as Sushil Jain at the Department of Pediatrics, Louisiana State University Medical Center, Shreveport.
In addition to conducting basic research designed to improve the outcome of pregnant women with diabetes, Joslin Diabetes Center also offers clinical care to mothers with diabetes. The Diabetes and Pregnancy program is a collaborative effort of the Joslin Clinic's medical staff and high-risk maternal-fetal medicine specialists at Beth Israel Deaconess Medical Center in Boston. Diabetes treatment is provided by the Joslin healthcare team, which includes physicians, nurse practitioners, nurse educators, dietitians and other diabetes specialists. Maternal fetal medicine specialists skilled in high-risk pregnancies provide the obstetrical care.
The Joslin Diabetes Center has a long legacy in research to improve the outcomes for women with diabetes. Dr. Priscilla White, one of the Center's early physicians, made significant contributions to this field by developing methods to improve the outcome of diabetic pregnancies beginning in the 1920s.
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