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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)
Forschungsdaten DOI PMC
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter PHGPx; redox metabolism; selenoprotein; spermatogenesis
Sprache englisch
Veröffentlichungsjahr 2009
HGF-Berichtsjahr 2009
ISSN (print) / ISBN 0892-6638
e-ISSN 1530-6860
Zeitschrift FASEB Journal
Quellenangaben Band: 23, Heft: 9, Seiten: 3233-3242 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Bethesda, Md.
Begutachtungsstatus Peer reviewed
Institut(e) 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)
POF Topic(s)
30204 - Cell Programming and Repair
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
Forschungsfeld(er)
Genetics and Epidemiology
Enabling and Novel Technologies
Immune Response and Infection
PSP-Element(e) G-501400-003
G-500500-001
G-500300-001
G-500600-003
G-501500-001
G-500390-001
PubMed ID 19417079
DOI 10.1096/fj.09-132795
Scopus ID 70349326728
Erfassungsdatum 2009-09-09
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