期刊
REPRODUCTIVE TOXICOLOGY
卷 69, 期 -, 页码 187-195出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.reprotox.2017.03.001
关键词
Polycyclic aromatic hydrocarbon; Kras; Puberty; Ovarian follicles; Mutation; Glutathione
资金
- National Institutes of Health (NIH) grant [R01ES020454]
- University of California Cancer Research Coordinating Committee, grant [CRR-12-201314]
- Center for Occupational and Environmental Health, UC Irvine
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 2 mg/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 Fl 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. (C) 2017 Elsevier Inc. All rights reserved.
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