Journal article
Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals
Nature genetics, Vol.28(4), pp.355-360
08/2001
Handle:
https://hdl.handle.net/2376/113203
PMID: 11455387
Abstract
Polycyclic aromatic hydrocarbons (PAHs) are toxic chemicals released into the environment by fossil fuel combustion. Moreover, a primary route of human exposure to PAHs is tobacco smoke. Oocyte destruction and ovarian failure occur in PAH-treated mice, and cigarette smoking causes early menopause in women. In many cells, PAHs activate the aromatic hydrocarbon receptor (Ahr), a member of the Per-Arnt-Sim family of transcription factors. The Ahr is also activated by dioxin, one of the most intensively studied environmental contaminants. Here we show that an exposure of mice to PAHs induces the expression of Bax in oocytes, followed by apoptosis. Ovarian damage caused by PAHs is prevented by Ahr or Bax inactivation. Oocytes microinjected with a Bax promoter-reporter construct show Ahr-dependent transcriptional activation after PAH, but not dioxin, treatment, consistent with findings that dioxin is not cytotoxic to oocytes. This difference in the action of PAHs versus dioxin is conveyed by a single base pair flanking each Ahr response element in the Bax promoter. Oocytes in human ovarian biopsies grafted into immunodeficient mice also accumulate Bax and undergo apoptosis after PAH exposure in vivo. Thus, Ahr-driven Bax transcription is a novel and evolutionarily conserved cell-death signaling pathway responsible for environmental toxicant-induced ovarian failure.
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Details
- Title
- Aromatic hydrocarbon receptor-driven Bax gene expression is required for premature ovarian failure caused by biohazardous environmental chemicals
- Creators
- Andrea Jurisicova - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School Samuel Lunenfeld Research Institute, Mount Sinai HospitalGloria I Perez - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical SchoolJonathan L Tilly - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical SchoolTiina Matikainen - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical SchoolRobert F Casper - Samuel Lunenfeld Research Institute, Mount Sinai HospitalJames K Pru - Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical SchoolHeui-Young Ryu - Department of Environmental Health, Boston University Schools of Medicine and Public HealthStanley J Korsmeyer - Howard Hughes Medical Institute, Departments of Pathology and Medicine, Dana-Farber Cancer Institute/Harvard Medical SchoolJennifer J Schlezinger - Department of Environmental Health, Boston University Schools of Medicine and Public HealthJarmo Laine - Division of Immunology, Beth Israel Deaconess Medical Center/Harvard Medical SchoolToshiyuki Sakai - Department of Preventive Medicine, Kyoto Prefectural University School of MedicineDavid H Sherr - Department of Environmental Health, Boston University Schools of Medicine and Public Health
- Publication Details
- Nature genetics, Vol.28(4), pp.355-360
- Academic Unit
- Animal Sciences, Department of
- Identifiers
- 99900547503301842
- Language
- English
- Resource Type
- Journal article