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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Effects of deletion of the transcription factor Nrf2 and benzo [a]pyrene treatment on ovarian follicles and ovarian surface epithelial cells in mice.

Authors: Lim, Jinhwan; Ortiz, Laura; Nakamura, Brooke N; Hoang, Yvonne D; Banuelos, Jesus; Flores, Victoria N; Chan, Jefferson Y; Luderer, Ulrike

Published In Reprod Toxicol, (2015 Dec)

Abstract: Polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP), are ubiquitous environmental pollutants and potent ovarian toxicants. The transcription factor NRF2 is an important regulator of the cellular response to electrophilic toxicants like BaP and to oxidative stress. NRF2 regulates transcription of genes involved in the detoxification of reactive metabolites of BaP and reactive oxygen species. We therefore hypothesized that Nrf2-/- mice have accelerated ovarian aging and increased sensitivity to the ovarian toxicity of BaP. A single injection of BaP dose-dependently depleted ovarian follicles in Nrf2+/+ and Nrf2-/- mice, but the effects of BaP were not enhanced in the absence of Nrf2. Similarly, Nrf2-/- mice did not have increased ovarian BaP DNA adduct formation compared to Nrf2+/+ mice. Ovarian follicle numbers did not differ between peripubertal Nrf2-/- and Nrf2+/+ mice, but by middle age, Nrf2-/- mice had significantly fewer primordial follicles than Nrf2+/+ mice, consistent with accelerated ovarian aging.

PubMed ID: 26247513 Exiting the NIEHS site

MeSH Terms: Animals; Antioxidants/metabolism; Apoptosis/drug effects; Benzo(a)pyrene/toxicity*; Cell Proliferation/drug effects; Cellular Senescence/drug effects*; DNA Adducts/metabolism; Dose-Response Relationship, Drug; Environmental Pollutants/toxicity*; Epithelial Cells/drug effects*; Epithelial Cells/metabolism; Epithelial Cells/pathology; Female; Gene Deletion*; Genotype; Mice, Inbred C57BL; Mice, Knockout; NF-E2-Related Factor 2/deficiency*; NF-E2-Related Factor 2/genetics; Ovarian Follicle/drug effects*; Ovarian Follicle/metabolism; Ovarian Follicle/pathology; Ovarian Reserve/drug effects; Ovary/drug effects*; Ovary/metabolism; Ovary/pathology; Oxidative Stress/drug effects; Phenotype

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