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 tumorigenesis by prenatal benzo[a]pyrene (BaP) exposure than Gclm+/+ mice. In the present study, the authors investigated effects of prenatal exposure to BaP on reproductive development and ovarian mutations in Kras, a commonly mutated gene in epithelial ovarian tumours. Pregnant mice 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. The authors observed no BaP treatment or Gclm genotype related differences in ovarian Kras codon 12 mutations in F1 offspring.
Authors: Luderer U, Myers MB, Banda M, McKim KL, Ortiz L, Parsons BL. ;Full Source: Reproductive Toxicology. 2017 Mar 6; 69:187-195. doi: 10.1016/j.reprotox.2017.03.001. [Epub ahead of print] ;