An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis

The primary recognised health risk from common deficiencies in glucose-6-ph osphate dehydrogenase (G6PD), a cytoprotective enzyme for oxidative stress, is red blood cell hemolysis. Here we show that litters from untreated preg nant mutant mice with a hereditary G6PD deficiency had increased prenatal d eath. When treated with the anticonvulsant drug phenytoin, a human teratoge n that is commonly used in pregnant women and causes embryonic oxidative st ress, G6PD-deficient dams had higher embryonic DNA oxidation and more fetal death and birth defects. The reported G6PD gene mutation was confirmed and used to genotype fetal resorptions, which were primarily G6PD deficient. T his is the first evidence that G6PD is a developmentally critical cytoprote ctive enzyme for both endogenous and xenobiotic-initiated embryopathic oxid ative stress and DNA damage. G6PD deficiencies accordingly may have a board er biological relevance as important determinants of infertility, in utero and postnatal death, and teratogenesis.