Title: Mitochondrial glutathione peroxidase 4 disruption causes male infertility
Abstract: The FASEB JournalVolume 23, Issue 9 p. 3233-3242 Research CommunicationFree to Read Mitochondrial glutathione peroxidase 4 disruption causes male infertility Manuela Schneider, Manuela Schneider Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, Germany Walter-Brendel-Centre for Experimental Medicine, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, D-81377 Munich, GermanySearch for more papers by this authorHeidi Forster, Heidi Forster Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorAuke Boersma, Auke Boersma Institute of Experimental Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorAlexander Seiler, Alexander Seiler Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorHelga Wehnes, Helga Wehnes Institute of Pathology, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorFred Sinowatz, Fred Sinowatz Department of Veterinary Anatomy II, Ludwig-Maximilians-University of Munich, Munich, GermanySearch for more papers by this authorChristine Neumüller, Christine Neumüller Department of Veterinary Anatomy II, Ludwig-Maximilians-University of Munich, Munich, GermanySearch for more papers by this authorManuel J. Deutsch, Manuel J. Deutsch Department of Gene Vectors, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorAxel Walch, Axel Walch Institute of Pathology, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorMartin Hrabe de Angelis, Martin Hrabe de Angelis Institute of Experimental Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorWolfgang Wurst, Wolfgang Wurst Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorFulvio Ursini, Fulvio Ursini Department of Biological Chemistry, University of Padua, Padova, ItalySearch for more papers by this authorAntonella Roveri, Antonella Roveri Department of Biological Chemistry, University of Padua, Padova, ItalySearch for more papers by this authorMarek Maleszewski, Marek Maleszewski Department of Embryology, Institute of Zoology, University of Warsaw, Warsaw, PolandSearch for more papers by this authorMatilde Maiorino, Matilde Maiorino Department of Biological Chemistry, University of Padua, Padova, ItalySearch for more papers by this authorMarcus Conrad, Corresponding Author Marcus Conrad [email protected] Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, GermanyCorrespondence: Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Marchioninistr. 25, D-81377 Munich, Germany. E-mail: [email protected]Search for more papers by this author Manuela Schneider, Manuela Schneider Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, Germany Walter-Brendel-Centre for Experimental Medicine, Ludwig-Maximilians-University of Munich, Marchioninistr. 15, D-81377 Munich, GermanySearch for more papers by this authorHeidi Forster, Heidi Forster Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorAuke Boersma, Auke Boersma Institute of Experimental Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorAlexander Seiler, Alexander Seiler Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorHelga Wehnes, Helga Wehnes Institute of Pathology, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorFred Sinowatz, Fred Sinowatz Department of Veterinary Anatomy II, Ludwig-Maximilians-University of Munich, Munich, GermanySearch for more papers by this authorChristine Neumüller, Christine Neumüller Department of Veterinary Anatomy II, Ludwig-Maximilians-University of Munich, Munich, GermanySearch for more papers by this authorManuel J. Deutsch, Manuel J. Deutsch Department of Gene Vectors, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorAxel Walch, Axel Walch Institute of Pathology, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorMartin Hrabe de Angelis, Martin Hrabe de Angelis Institute of Experimental Genetics, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorWolfgang Wurst, Wolfgang Wurst Institute of Developmental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, GermanySearch for more papers by this authorFulvio Ursini, Fulvio Ursini Department of Biological Chemistry, University of Padua, Padova, ItalySearch for more papers by this authorAntonella Roveri, Antonella Roveri Department of Biological Chemistry, University of Padua, Padova, ItalySearch for more papers by this authorMarek Maleszewski, Marek Maleszewski Department of Embryology, Institute of Zoology, University of Warsaw, Warsaw, PolandSearch for more papers by this authorMatilde Maiorino, Matilde Maiorino Department of Biological Chemistry, University of Padua, Padova, ItalySearch for more papers by this authorMarcus Conrad, Corresponding Author Marcus Conrad [email protected] Institute of Clinical Molecular Biology and Tumor Genetics, German Research Center for Environmental Health, Neuherberg, GermanyCorrespondence: Institute of Clinical Molecular Biology and Tumor Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Marchioninistr. 25, D-81377 Munich, Germany. E-mail: [email protected]Search for more papers by this author First published: 05 May 2009 https://doi.org/10.1096/fj.09-132795Citations: 212Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat ABSTRACT 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.—Schneider, M., Forster, H., Boersma, A., Seiler, A., Wehnes, H., Sinowatz, F., Neumüller, C., Deutsch, M. J., Walch, A., Hrabede Angelis, M., Wurst, W., Ursini, F., Roveri, A., Maleszewski, M., Maiorino, M. Conrad, M. Mitochondrial glutathione peroxidase 4 disruption causes male infertility. FASEB J. 23, 3233–3242 (2009). www.fasebj.org Supporting Information Filename Description fsb2fj09132795-sup-0001.zipZip archive, 6.5 MB Supplementary Material 1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. REFERENCES 1Jacobsson, S. O., and Hansson, E. 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Publication Year: 2009
Publication Date: 2009-05-05
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 283
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