title: An embryoprotective role for glucose-6-phosphate dehydrogenase in developmental oxidative stress and chemical teratogenesis.
abstract: The primary recognized health risk from common deficiencies in glucose-6-phosphate dehydrogenase (G6PD), a cytoprotective enzyme for oxidative stress, is red blood cell hemolysis. Here we show that litters from untreated pregnant mutant mice with a hereditary G6PD deficiency had increased prenatal (fetal resorptions) and postnatal death. When treated with the anticonvulsant drug phenytoin, a human teratogen that is commonly used in pregnant women and causes embryonic oxidative stress, 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. This is the first evidence that G6PD is a developmentally critical cytoprotective enzyme for both endogenous and xenobiotic-initiated embryopathic oxidative stress and DNA damage. G6PD deficiencies accordingly may have a broader biological relevance as important determinants of infertility, in utero and postnatal death, and teratogenesis.
authors.affiliation: Department of Pharmacology, University of Toronto, Medical Sciences Building, Toronto Ontario, Canada M5S 1A8.
authors.forename: C J
authors.initials: CJ
authors.lastname: Nicol
authors.forename: J
authors.initials: J
authors.lastname: Zielenski
authors.forename: L C
authors.initials: LC
authors.lastname: Tsui
authors.forename: P G
authors.initials: PG
authors.lastname: Wells
mesh_terms: D000818:Animals; D001483:Base Sequence; D004249:DNA Damage; D017931:DNA Primers; D004622:Embryo, Mammalian / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000502:physiology*; D006579:Heterozygote; D006720:Homozygote; D051379:Mice; D008817:Mice, Mutant Strains; D018384:Oxidative Stress; D010641:Phenotype; D011247:Pregnancy; D013723:Teratogens / Q000494:pharmacology*
chemical_list: D017931:DNA Primers; D013723:Teratogens; D005954:Glucosephosphate Dehydrogenase