New Facts on Birth Defect Cause in Diabetic Mothers

Oxygen and glucose supply of the
foetus seems to play a major role
in birth defects; © PHIL

The babies of women with diabetes are two to five times more likely to develop birth defects than offspring of women without the disease. In the new study, Dr. Mary R. Loeken at the Diabetes Center in Boston and her colleagues examined embryos of pregnant mice injected with glucose to mimic diabetic pregnancy.

Working in collaboration with Peter Smith, Ph.D., Director of the BioCurrents Research Center at the Marine Biological Laboratory at Woods Hole, Mass., Loeken found that the oxygen concentrations in embryos of mice injected with glucose were significantly lower than in control embryos. This demonstrated that breaking down higher amounts of glucose caused oxygen to be used up faster than it could be delivered.

The researchers then injected pregnant mice with glucose, or exposed them to varying levels of oxygen to see if raising and lowering oxygen delivery to the embryos had the same effect as raising and lowering glucose. The scientists' goal was to see whether oxygen deprivation is what mediates the effects of high glucose on the embryo in pregnant diabetic mice. Loeken's lab had previously found that inducing high blood glucose levels in pregnant mice suppressed Pax3 expression in embryos. Pax3 is a gene required for healthy formation of the brain and spinal cord.

The researchers found that restricting oxygen delivery had the same effect as high glucose. In fact, embryos from pregnant mice with high blood glucose levels, or oxygen-restricted mice, had five-fold decreases in Pax3 expression and eight-fold increases in a severe type of birth defect called neural tube defects. Conversely, increasing the oxygen delivery to pregnant diabetic mice blocked the decrease in Pax3 expression and neural tube defects in their embryos.

The results suggest that the lack of oxygen caused by increased glucose consumption triggers the production of free radicals, which then causes birth defects, Loeken explains.; Source: Joslin Diabetes Center