title: Ovarian effects of prenatal exposure to benzo[a]pyrene: Roles of embryonic and maternal glutathione status.
abstract: Females deficient in the glutamate cysteine ligase modifier subunit (Gclm) of the rate-limiting enzyme in glutathione synthesis are more sensitive to ovarian follicle depletion and tumorigenesisby prenatal benzo[a]pyrene (BaP) exposure than Gclm+/+ mice. We investigated effects of prenatal exposure to BaP on reproductive development and ovarian mutations in Kras, a commonly mutated gene in epithelial ovarian tumors. Pregnantmice were dosed from gestational day 6.5 through 15.5 with 2mg/kg/day BaP or vehicle. Puberty onset occurred 5 days earlier in F1 daughters of all Gclm genotypes exposed to BaP compared to controls. Gclm+/- F1 daughters of Gclm+/- mothers and wildtype F1 daughters of wildtype mothers had similar depletion of ovarian follicles following prenatal exposure to BaP, suggesting that maternal Gclm genotype does not modify ovarian effects of prenatal BaP. We observed no BaP treatment or Gclm genotype related differences in ovarian Kras codon 12 mutations in F1 offspring.
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Medicine, University of California Irvine, Irvine, CA 92617, United States; Department of Developmental and Cell Biology, UC Irvine, Irvine, CA 92617, United States; Program in Public Health, UC Irvine, Irvine, CA 92617, United States. Electronic address: uluderer@uci.edu.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Luderer
authors.affiliation: U.S. Food, Drug Administration, Division of Genetic, Reproductive Toxicology, National Center for Toxicological Research, Jefferson, AR, United States.
authors.forename: Meagan B
authors.initials: MB
authors.lastname: Myers
authors.affiliation: U.S. Food, Drug Administration, Division of Genetic, Reproductive Toxicology, National Center for Toxicological Research, Jefferson, AR, United States. Electronic address: Malathi.Banda@covance.com.
authors.forename: Malathi
authors.initials: M
authors.lastname: Banda
authors.affiliation: U.S. Food, Drug Administration, Division of Genetic, Reproductive Toxicology, National Center for Toxicological Research, Jefferson, AR, United States.
authors.forename: Karen L
authors.initials: KL
authors.lastname: McKim
authors.affiliation: Division of Occupational and Environmental Medicine, Department of Medicine, University of California Irvine, Irvine, CA 92617, United States.
authors.forename: Laura
authors.initials: L
authors.lastname: Ortiz
authors.affiliation: U.S. Food, Drug Administration, Division of Genetic, Reproductive Toxicology, National Center for Toxicological Research, Jefferson, AR, United States.
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Parsons
mesh_terms: D000818:Animals; D001564:Benzo(a)pyrene / Q000633:toxicity*; D005260:Female; D011905:Genes, ras; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D005978:Glutathione / Q000378:metabolism; D008431:Maternal-Fetal Exchange; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009154:Mutation; D010053:Ovary / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012741:Sexual Maturation / Q000187:drug effects
chemical_list: D001564:Benzo(a)pyrene; C560749:GCLM protein, mouse; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Glutathione; Kras; Mutation; Ovarian follicles; Polycyclic aromatic hydrocarbon; Puberty