دورية أكاديمية
Mitochondrial glutathione peroxidase 4 disruption causes male infertility.
| العنوان: | Mitochondrial glutathione peroxidase 4 disruption causes male infertility. |
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| المؤلفون: | Schneider M; Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany., Förster H, Boersma A, Seiler A, Wehnes H, Sinowatz F, Neumüller C, Deutsch MJ, Walch A, Hrabé de Angelis M, Wurst W, Ursini F, Roveri A, Maleszewski M, Maiorino M, Conrad M |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2009 Sep; Vol. 23 (9), pp. 3233-42. Date of Electronic Publication: 2009 May 05. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Glutathione Peroxidase/*physiology , Infertility, Male/*etiology , Mitochondrial Proteins/*physiology, Animals ; Apoptosis ; Embryonic Development ; Glutathione Peroxidase/deficiency ; Male ; Mice ; Phospholipid Hydroperoxide Glutathione Peroxidase ; Selenium/physiology ; Spermatozoa/pathology |
| مستخلص: | Selenium is linked to male fertility. Glutathione peroxidase 4 (GPx4), first described as an antioxidant enzyme, is the predominant selenoenzyme in testis and has been suspected of being vital for spermatogenesis. Cytosolic, mitochondrial, and nuclear isoforms are all encoded by the same gene. While disruption of entire GPx4 causes early embryonic lethality in mice, inactivation of nuclear GPx4 does not impair embryonic development or fertility. Here, we show that deletion of mitochondrial GPx4 (mGPx4) allows both normal embryogenesis and postnatal development, but causes male infertility. Infertility was associated with impaired sperm quality and severe structural abnormalities in the midpiece of spermatozoa. Knockout sperm display higher protein thiol content and recapitulate features typical of severe selenodeficiency. Interestingly, male infertility induced by mGPx4 depletion could be bypassed by intracytoplasmic sperm injection. We also show for the first time that mGPx4 is the prevailing GPx4 product in male germ cells and that mGPx4 disruption has no effect on proliferation or apoptosis of germinal or somatic tissue. Our study finally establishes that mitochondrial GPx4 confers the vital role of selenium in mammalian male fertility and identifies cytosolic GPx4 as the only GPx4 isoform being essential for embryonic development and apoptosis regulation. |
| المشرفين على المادة: | 0 (Mitochondrial Proteins) EC 1.11.1.12 (Phospholipid Hydroperoxide Glutathione Peroxidase) EC 1.11.1.9 (Glutathione Peroxidase) H6241UJ22B (Selenium) |
| تواريخ الأحداث: | Date Created: 20090507 Date Completed: 20091023 Latest Revision: 20191210 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1096/fj.09-132795 |
| PMID: | 19417079 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.09-132795 |