Selenium in mammalian spermiogenesis
-
Leopold Flohé
Abstract
The role of selenium in male fertility is reviewed with special emphasis on selenoprotein P and phospholipid hydroperoxide glutathione peroxidase (GPx4) in spermiogenesis. Inverse genetics reveal that selenoprotein P is required for selenium supply to the testis. GPx4 is abundantly synthesized in spermatids. As a moonlighting protein it is transformed in the later stages of spermiogenesis from an active selenoperoxidase into a structural protein that becomes a constituent of the mitochondrial sheath of spermatozoa. The transformation is paralleled by loss of glutathione. Mechanistically, the process is an alternate substrate inactivation of GPx4 resulting from reactions of its selenenic form with thiols of GPx4 itself and other proteins. Circumstantial evidence and ongoing experimental genetics indicate that the mitochondrially expressed form of the GPx4 gene is the most relevant one in spermiogenesis, with the nuclear form being dispensable for fertility and the role of cytosolic GPx4 remaining unclear. Clinical data reveal a strong association of low sperm GPx4 with infertility. Thus, impaired GPx4 biosynthesis, due to selenium deficiency or to genetic defects in gpx4 itself or in proteins involved in Se distribution and selenoprotein biosynthesis, causes male infertility, but can also be an epiphenomenon due to any perturbation of testicular function.
©2007 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Selenoproteins – biochemistry and clinical relevance
- Selenium in mammalian spermiogenesis
- Selenium in chemistry and biochemistry in comparison to sulfur
- Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function
- Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals
- Activation of the glutathione peroxidase 2 (GPx2) promoter by β-catenin
- Effect of age on sexually dimorphic selenoprotein expression in mice
- Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells
- Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3
- Towards understanding selenocysteine incorporation into bacterial proteins
- Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
- B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance
- Effect of selenium on thioredoxin reductase activity in Txnrd1 or Txnrd2 hemizygous mice
- Influence of pH and flanking serine on the redox potential of S-S and S-Se bridges of Cys-Cys and Cys-Sec peptides
- An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors
- Glucocorticoid receptor-mediated expression of kallikrein 10 in human breast cancer cell lines
Articles in the same Issue
- Selenoproteins – biochemistry and clinical relevance
- Selenium in mammalian spermiogenesis
- Selenium in chemistry and biochemistry in comparison to sulfur
- Molecular biology of glutathione peroxidase 4: from genomic structure to developmental expression and neural function
- Physiological role of phospholipid hydroperoxide glutathione peroxidase in mammals
- Activation of the glutathione peroxidase 2 (GPx2) promoter by β-catenin
- Effect of age on sexually dimorphic selenoprotein expression in mice
- Post-translational processing of selenoprotein P: implications of glycosylation for its utilisation by target cells
- Selenoproteins of the thyroid gland: expression, localization and possible function of glutathione peroxidase 3
- Towards understanding selenocysteine incorporation into bacterial proteins
- Glutathione- and thioredoxin-related enzymes are modulated by sulfur-containing chemopreventive agents
- B- and T-cell-specific inactivation of thioredoxin reductase 2 does not impair lymphocyte development and maintenance
- Effect of selenium on thioredoxin reductase activity in Txnrd1 or Txnrd2 hemizygous mice
- Influence of pH and flanking serine on the redox potential of S-S and S-Se bridges of Cys-Cys and Cys-Sec peptides
- An essential role for Pin1 in Xenopus laevis embryonic development revealed by specific inhibitors
- Glucocorticoid receptor-mediated expression of kallikrein 10 in human breast cancer cell lines
