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Molecular and Cellular Biology, September 2005, p. 7637-7644, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7637-7644.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Nuclear Form of Phospholipid Hydroperoxide Glutathione Peroxidase Is a Protein Thiol Peroxidase Contributing to Sperm Chromatin Stability

Institute of Clinical Molecular Biology and Tumour Genetics, GSF Research Centre for Environment and Health, Marchioninistr. 25, D-81377 Munich, Germany,¹ Department of Comparative Medicine, GSF Research Centre for Environment and Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany,² UMR Gamétogenèse et Génotoxicité, CEA, INSERM U566, Université Paris 7, F-92265 Fontenay-aux-Roses, France,³ Department of Veterinary Anatomy II, Ludwig-Maximilian University of Munich, Veterinärstraße 13, D-80539 Munich, Germany,⁴ Department of Biological Chemistry, University of Padova, Viale G. Colombo, 3, I-35121 Padova, Italy,⁵ Institute of Developmental Genetics, GSF Research Centre for Environment and Health, Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany⁶

Received 20 January 2005/ Returned for modification 5 April 2005/ Accepted 7 June 2005

The selenoenzyme phospholipid hydroperoxide glutathione peroxidase (PHGPx) is regarded as the major molecular target of selenodeficiency in rodents, accounting for most of the histopathological and structural abnormalities of testicular tissue and male germ cells. PHGPx exists as a cytosolic form, mitochondrial form, and nuclear form (nPHGPx) predominantly expressed in late spermatids and spermatozoa. Here, we demonstrate that mice with a targeted deletion of the nPHGPx gene were, unlike mice with the full knockout (KO) of PHGPx, not only viable but also, surprisingly, fully fertile. While both morphological analysis of testis and epididymis and sperm parameter measurements did not show any apparent abnormality, toluidine blue and acridine orange stainings of spermatozoa indicated defective chromatin condensation in the KO sperm isolated from the caput epididymis. Furthermore, upon drying and hydrating, KO sperm exhibited a significant proportion of morphologically abnormal heads. Monobromobimane labeling and protein-free thiol titration revealed significantly less extensive oxidation in the cauda epididymis when compared to that in the wild type. We conclude that nPHGPx, by acting as a protein thiol peroxidase in vivo, contributes to the structural stability of sperm chromatin.

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