Effects of deletion of the transcription factor Nrf2 and benzo [a]pyrene treatment on ovarian follicles and ovarian surface epithelial cells in mice |
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| Affiliation: | 1. MOE Laboratory for Earth Surface Processes, College of Urban & Environmental Sciences, Peking University, Beijing 100871, China;2. State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing 100012, China;3. Section of Toxicology and Environmental Chemistry, Institute A, University of Copenhagen, University Park 2, DK 2100, Copenhagen Ø, Denmark;1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam 781032, India;2. Department of Pharmacology and Toxicology, College of Veterinary Science, Assam Agricultural University, Guwahati, Assam 781032, India;3. State Biotech Hub, College of Veterinary Science, Assam Agricultural University, Khanapara, Guwahati, Assam 781022, India |
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| 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. |
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| Keywords: | NRF2 Ovarian aging Benzo[a]pyrene Oxidative stress Polycyclic aromatic hydrocarbon DNA adduct |
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