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Common enzyme deficiency may jeopardize pregnancies

A hereditary enzyme deficiency increases the incidence of fetal death and birth defects in mice, a discovery that may have implications for the over 400 million people around the world who have the condition, says a study published in the January issue of The Federation of American Societies for Experimental Biology Journal.

The study found the first evidence that the enzyme, glucose-6-phosphate dehydrogenase (G6PD), is critical to the healthy development of embryos. Without G6PD, embryonic cells are susceptible to damage caused by reactive oxygen species -- or free radicals -- that occur as a result of normal development or the introduction of certain drugs and environmental chemicals during pregnancy. In people without the deficiency, G6PD is an antioxidant enzyme that protects cells from the harmful effects of these normal and drug-enhanced oxidative stresses.

The researchers compared the pregnancies of mutant mice with various degrees of G6PD deficiency to normal mice and found higher rates of prenatal and postnatal death in the deficient group. Another group of mutant mice was treated with a drug known to create oxidative stress called phenytoin, the most common anti-epileptic drug in North America. Phenytoin's oxidant effect is comparable to that of many other drugs and chemicals in the environment.

"Even without any treatment at all, mouse embryos that were deficient in the enzyme were more likely to suffer just from the oxidative stress that happens naturally during development," says co-author Peter Wells of the University of Toronto's Faculty of Pharmacy. "Then when we exposed them to a drug that produces reactive oxygen species, the embryonic death rates and incidence of birth defects in the surviving fetuses went through the roof, although the mothers remained healthy. The next question is, will we find the same results in humans?" Until now, Wells says, the only health risk associated with the deficiency was the premature destru
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Contact: Megan Easton
megan.easton@utoronto.ca
416-978-5948
University of Toronto
2-Jan-2000


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