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Schneider, M. ; Förster, H. ; Boersma, A. ; Seiler, A. ; Wehnes, H. ; Sinowatz, F.* ; Neumüller, C.* ; Deutsch, M.J. ; Walch, A.K. ; Hrabě de 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)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords PHGPx; redox metabolism; selenoprotein; spermatogenesis
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Journal FASEB Journal
Quellenangaben Volume: 23, Issue: 9, Pages: 3233-3242 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Bethesda, Md.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
Institute of Developmental Genetics (IDG)
Institute of Pathology (PATH)
Institute of Experimental Genetics (IEG)
Research Unit Gene Vector (AGV)
Research Unit Analytical Pathology (AAP)