title: Effects of deletion of the transcription factor Nrf2 and benzo [a]pyrene treatment on ovarian follicles and ovarian surface epithelial cells in mice.
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.
authors.affiliation: Department of Medicine, University of California Irvine, USA.
authors.forename: Jinhwan
authors.initials: J
authors.lastname: Lim
authors.affiliation: Department of Medicine, University of California Irvine, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Ortiz
authors.affiliation: Department of Medicine, University of California Irvine, USA.
authors.forename: Brooke N
authors.initials: BN
authors.lastname: Nakamura
authors.affiliation: Department of Medicine, University of California Irvine, USA.
authors.forename: Yvonne D
authors.initials: YD
authors.lastname: Hoang
authors.affiliation: Department of Medicine, University of California Irvine, USA.
authors.forename: Jesus
authors.initials: J
authors.lastname: Banuelos
authors.affiliation: Department of Medicine, University of California Irvine, USA.
authors.forename: Victoria N
authors.initials: VN
authors.lastname: Flores
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Irvine, USA.
authors.forename: Jefferson Y
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Department of Medicine, University of California Irvine, USA; Department of Developmental and Cell Biology, University of California Irvine, USA. Electronic address: uluderer@uci.edu.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Luderer
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001564:Benzo(a)pyrene / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D018736:DNA Adducts / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000172:deficiency* / Q000235:genetics; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D065851:Ovarian Reserve / Q000187:drug effects; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D010641:Phenotype
chemical_list: D000975:Antioxidants; D018736:DNA Adducts; D004785:Environmental Pollutants; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D001564:Benzo(a)pyrene
keywords: Benzo[a]pyrene; DNA adduct; NRF2; Ovarian aging; Oxidative stress; Polycyclic aromatic hydrocarbon