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Selenium, a Key Element in Spermatogenesis and Male Fertility

  • Carla Boitani
  • Rossella Puglisi
Part of the Advances in Experimental Medicine and Biology book series (volume 636)

Abstract

Selenium is essential for normal spermatogenesis of mammals and its critical role is mainly mediated by two selenoproteins, namely phospholipid hydroperoxide glutathione peroxidase (PHGPx/GPx4) and Selenoprotein P. PHGPx/GPx4 is the major selenoprotein expressed by germ cells in the testis, having multiple functions and representing the pivotal link between selenium, sperm quality and male fertility. Selenoprotein P is a plasma protein that is required for selenium supply to the testis. In the last years, nutritional studies and experimental animal models lacking/overexpressing a specific PHGPx isoform and selenoprotein P have highly expanded our understanding on how the male reproductive system depends on selenium. The focus of this review, is to report and discuss the most relevant and recent findings in this field. Clinical data have pointed to a correlation between abnormal PHGPx content in sperm and disturbance of human male fertility. However, additional evidence is still required to draw any definitive conclusions about therapeutical strategies for improving fertility by selenium administration.

Keywords

Male Fertility Male Germ Cell Selenium Deficiency Epididymal Spermatozoon Male Gonad 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Behne D, Hofer T, Berswordt-Wallrabe R et al. Selenium in the testis of the rat: Studies on its regulation and its importance for the organism. J Nutr 1982; 112(9):1682–1687.PubMedGoogle Scholar
  2. 2.
    Burk RF, Hill KE, Motley AK. Selenoprotein metabolism and function: Evidence for more than one function for selenoprotein P. J Nutr 2003; 133(5 Suppl 1):1517S–1520S.PubMedGoogle Scholar
  3. 3.
    Hoffmann PR, Hoge SC, Li PA et al. The selenoproteome exhibits widely varying, tissue-specific dependence on selenoprotein P for selenium supply. Nucleic Acids Res 2007; 35(12):3963–3973.CrossRefPubMedGoogle Scholar
  4. 4.
    Su D, Novoselov, SV, Sun QA et al. Mammalian selenoprotein thioredoxin-glutathione reductase: Roles in disulfide bond formation and sperm maturation. J Biol Chem 2005; 280(28):26491–26498.CrossRefPubMedGoogle Scholar
  5. 5.
    Kryukov GV, Castellano S, Novoselov SV et al. Characterization of mammalian selenoproteo mes Science 2003; 300(5624):1439–1443.CrossRefPubMedGoogle Scholar
  6. 6.
    Koga M, Tanaka H, Yomogida K et al. Expression of selenoprotein-P messenger ribonucleic acid in the rat testis. Biol Reprod 1998; 58(1):261–265.CrossRefPubMedGoogle Scholar
  7. 7.
    Olson GE, Winfrey VP, Nagdas SK et al. Selenoprotein P is required for mouse sperm development. Biol Reprod 2005; 73(1):201–211.CrossRefPubMedGoogle Scholar
  8. 8.
    Mihara H, Kurihara T, Watanabe T et al. cDNA cloning, purification, and characterization of mouse liver selenocysteine lyase: Candidate for selenium delivery protein in selenoprotein synthesis. J Biol Chem 2000; 275(9):6195–6200.CrossRefPubMedGoogle Scholar
  9. 9.
    Ursini F, Maiorino M, Valente M et al. Purification from pig liver of a protein which protects liposomes and biomembranes from peroxidative degradation and exhibits glutathione peroxidase activity on phosphatidylcholine hydroperoxides. Biochim Biophys Acta 1982; 710(2):197–211.PubMedGoogle Scholar
  10. 10.
    Godeas C, Tramer F, Micali F et al. Distribution and possible novel role of phospholipid hydroperoxide glutathione peroxidase in rat epididymal spermatozoa. Biol Reprod 1997; 57(6):1502–1508.CrossRefPubMedGoogle Scholar
  11. 11.
    Maiorino M, Scapin M, Ursini F et al. Distinct promoters determine alternative transcription of gpx-4 into phospholipid-hydroperoxide glutathione peroxidase variants. J Biol Chem 2003; 278(36):34286–34290.CrossRefPubMedGoogle Scholar
  12. 12.
    Ursini F, Maiorino M, Brigelius-Flohe R et al. Diversity of glutathione peroxidases. Methods Enzymol 1995; 252:38–53.CrossRefPubMedGoogle Scholar
  13. 13.
    Borchert A, Wang CC, Ufer C et al. The role of phospholipid hydroperoxide glutathione peroxidase isoforms in murine embryogenesis. J Biol Chem 2006; 281(28):19655–19664.CrossRefPubMedGoogle Scholar
  14. 14.
    Roveri A, Casasco A, Maiorino M et al. Phospholipid hydroperoxide glutathione peroxidase of rat testis. Gonadotropin dependence and immunocytochemical identification. J Biol Chem 1992; 267(9):6142–6146.PubMedGoogle Scholar
  15. 15.
    Maiorino M, Wissing JB, Brigelius-Flohe R et al. Testosterone mediates expression of the selenoprotein PHGPx by induction of spermatogenesis and not by direct transcriptional gene activation. FASEB J 1998; 12(13):1359–1370.PubMedGoogle Scholar
  16. 16.
    Puglisi R, Tramer F, Panfili E et al. Differential splicing of the phospholipid hydroperoxide glutathione peroxidase gene in diploid and haploid male germ cells in the rat. Biol Reprod 2003; 68(2):405–411.CrossRefPubMedGoogle Scholar
  17. 17.
    Tramer F, Micali F, Sandri G et al. Enzymatic and immunochemical evaluation of phospholipid hydroperoxide glutathione peroxidase (PHGPx) in testes and epididymal spermatozoa of rats of different ages. Int J Androl 2002; 25(2):72–83.CrossRefPubMedGoogle Scholar
  18. 18.
    Borchert A, Savaskan NE, Kuhn H. Regulation of expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. Tissue-specific expression pattern and identification of functional cis-and trans-regulatory elements. J Biol Chem 2003; 278(4):2571–2580.CrossRefPubMedGoogle Scholar
  19. 19.
    Tramer F, Vetere A, Martinelli M et al. cAMP-response element modulator-tau activates a distinct promoter element for the expression of the phospholipid hydroperoxide/sperm nucleus glutathione peroxidase gene. Biochem J 2004; 383(Pt 1):179–185.PubMedGoogle Scholar
  20. 20.
    Lenzi A, Gandini L, Picardo M et al. Lipoperoxidation damage of spermatozoa polyunsaturated fatty acids (PUFA): Scavenger mechanisms and possible scavenger therapies. Front Biosci 2000; 5:E1–E15.CrossRefPubMedGoogle Scholar
  21. 21.
    Ursini F, Heim S, Kiess M et al. Dual function, of the selenoprotein PHGPx during sperm maturation. Science 1999; 285(5432):1393–1396.CrossRefPubMedGoogle Scholar
  22. 22.
    Wu AS, Oldfield JE, Shull LR et al. Specific effect of selenium deficiency on rat sperm. Biol Reprod 1979; 20(4):793–798.CrossRefPubMedGoogle Scholar
  23. 23.
    Imai H, Suzuki K, Ishizaka K et al. Failure of the expression of phospholipid hydroperoxide glutathione peroxidase in the spermatozoa of human infertile males. Biol Reprod 2001; 64(2):674–683.CrossRefPubMedGoogle Scholar
  24. 24.
    Foresta C, Flohe L, Garolla A et al. Male fertility is linked to the selenoprotein phospholipid hydroperoxide glutathione peroxidase. Biol Reprod 2002; 67(3):967–971.CrossRefPubMedGoogle Scholar
  25. 25.
    Tramer F, Caponecchia L, Sgro P et al. Native specific activity of glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo-and hypomotile human sperm samples. Int J Androl 2004; 27(2):88–93.CrossRefPubMedGoogle Scholar
  26. 26.
    Conrad M, Moreno SG, Sinowatz F et al. The nuclear form of phospholipid hydroperoxide glutathione peroxidase is a protein thiol peroxidase contributing to sperm chromatin stability. Mol cell Biol 2005; 25(17):7637–7644.CrossRefPubMedGoogle Scholar
  27. 27.
    Watanabe T, Endo A. Effects of selenium deficiency on sperm morphology and spermatocyte chromosomes in mice. Mutat Res 1991; 262(2):93–99.CrossRefPubMedGoogle Scholar
  28. 28.
    Pfeifer H, Conrad M, Roethlein D et al. Identification of a specific sperm nuclei selenoenzyme necessary for protamine thiol cross-linking during sperm maturation. FASEB J 2001; 15(7):1236–1238.PubMedGoogle Scholar
  29. 29.
    Shalgi R, Seligman J, Kosower NS. Dynamics of the thiol status of rat spermatozoa during maturation: Analysis with the fluorescent labeling agent monobromobimane. Biol Reprod 1989; 40(5):1037–1045.CrossRefPubMedGoogle Scholar
  30. 30.
    Seligman J, Newton GL, Fahey RC et al. Nonprotein thiols and disulfides in rat epididymal spermatozoa and epididymal fluid: Role of gamma-glutamyl-transpeptidase in sperm maturation. J Androl 2005; 26(5):629–637.CrossRefPubMedGoogle Scholar
  31. 31.
    Imai H, Hirao F, Sakamoto T et al. Early embryonic lethality caused by targeted disruption of the mouse PHGPx gene. Biochem Biophys Res Commun 2003; 305(2):278–286.CrossRefPubMedGoogle Scholar
  32. 32.
    Yant LJ, Ran Q, Rao L et al. The selenoprotein GPX4 is essential for mouse development and protects from radiation and oxidative damage insults. Free Radic Biol Med 2003; 34(4):496–502.CrossRefPubMedGoogle Scholar
  33. 33.
    Sage J, Martin L, Meuwissen R et al. Temporal and spatial control of the Sycp1 gene transcription in the mouse meiosis: Regulatory elements active in the male are not sufficient for expression in the female gonad. Mech Dev 1999; 80(1):29–39.CrossRefPubMedGoogle Scholar
  34. 34.
    Puglisi R, Bevilacqua A, Carlomagno G et al. Mice overexpressing the mitochondrial phospholipid hydroperoxide glutathione peroxidase in male germ cells show abnormal spermatogenesis and reduced fertility. Endocrinology 2007; 148(9):4302–4309.CrossRefPubMedGoogle Scholar
  35. 35.
    Hill KE, Zhou J, McMahan WJ et al. Deletion of selenoprotein P alters distribution of selenium in the mouse. J Biol Chem 2003; 278(16):13640–13646.CrossRefPubMedGoogle Scholar
  36. 36.
    Schomburg L, Schweizer U, Holtmann B et al. Gene disruption discloses role of selenoprotein P in selenium delivery to target tissues. Biochem J 2003; 370(Pt. 2):397–402.CrossRefPubMedGoogle Scholar
  37. 37.
    Hill KE, Zhou J, Austin LM et al. The selenium-rich C-terminal domain of mouse selenoprotein P is necessary for the supply of selenium to brain and testis but not for the maintenance of whole body selenium. J Biol Chem 2007; 282(15):10972–10980.CrossRefPubMedGoogle Scholar
  38. 38.
    Olson GE, Winfrey VP, Hill KE et al. Sequential development of flagellar defects in spermatids and epididymal spermatozoa of selenium-deficient rats. Reproduction 2004; 127(3):335–342.CrossRefPubMedGoogle Scholar
  39. 39.
    Renko K, Werner M, Renner-Muller I et al. Hepatic selenoprotein P (Sepp) expression restores selenium transport and prevents infertility and motor-incoordination in Sepp-knockout mice. Biochem J 2007.Google Scholar
  40. 40.
    Olson GE, Winfrey VP, Nagdas SK et al. Apolipoprotein E receptor-2 (ApoER2) mediates selenium uptake from selenoprotein P by the mouse testis. J Biol Chem 2007; 282(16):12290–12297.CrossRefPubMedGoogle Scholar
  41. 41.
    Andersen OM, Yeung CH, Vorum H et al. Essential role of the apolipoprotein E receptor-2 in sperm development. J Biol Chem 2003; 278(26):23989–23995.CrossRefPubMedGoogle Scholar
  42. 42.
    Atkinson JB, Hill KE, Burk RF. Centrilobular endothelial cell injury by diquat in the selenium-deficient rat liver. Lab Invest 2001; 81(2):193–200.PubMedGoogle Scholar
  43. 43.
    Burk RF, Hill KE, Awad JA et al. Pathogenesis of diquat-induced liver necrosis in selenium-deficient rats: Assessment of the roles of lipid peroxidation and selenoprotein P. Hepatology 1995; 21(2):561–569.PubMedGoogle Scholar
  44. 44.
    Wu SH, Oldfield JE, Whanger PD et al. Effect of selenium, vitamin E, and antioxidants on testicular function in rats. Biol Reprod 1973; 8(5):625–629.PubMedGoogle Scholar
  45. 45.
    Behne D, Weiler H, Kyriakopoulos A. Effects of selenium deficiency on testicular morphology and function in rats. J Reprod Fertil 1996; 106(2):291–297.PubMedCrossRefGoogle Scholar
  46. 46.
    Shalini S, Bansal MP. Dietary selenium deficiency as well as excess supplementation induces multiple defects in mouse epididymal spermatozoa: Understanding the role of selenium in male fertility. Int J Androl 2007.Google Scholar
  47. 47.
    Shalini S, Bansal MP. Alterations in selenium status influences reproductive potential of male mice by modulation of transcription factor NFkappaB. Biometals 2007; 20(1):49–59.CrossRefPubMedGoogle Scholar
  48. 48.
    Shalini S, Bansal MP. Role of selenium in regulation of spermatogenesis: Involvement of activator protein 1. Biofactors 2005; 23(3):151–162.CrossRefPubMedGoogle Scholar
  49. 49.
    Kaur P, Bansal MP. Effect of selenium-induced oxidative stress on the cell kinetics in testis and reproductive ability of male mice. Nutrition 2005; 21(3):351–357.CrossRefPubMedGoogle Scholar
  50. 50.
    Brigelius-Flohe R. Glutathione peroxidases and redox-regulated transcription factors. Biol Chem 2006; 387(10–11):1329–1335.CrossRefPubMedGoogle Scholar
  51. 51.
    Ten J, Vendrell FJ, Cano A et al. Dietary antioxidant supplementation did not affect declining sperm function with age in the mouse but did increase head abnormalities and reduced sperm production. Reprod Nutr Dev 1997; 37(5):481–492.CrossRefPubMedGoogle Scholar
  52. 52.
    Kohrle J, Jakob F, Contempre B et al. Selenium, the thyroid, and the endocrine system. Endocr Rev 2005; 26(7):944–984.CrossRefPubMedGoogle Scholar
  53. 53.
    Scott R, MacPherson A, Yates RW et al. The effect of oral selenium supplementation on human sperm motility. Br J Urol 1998; 82(1):76–80.PubMedGoogle Scholar
  54. 54.
    Maiorino M, Bosello V, Ursini F et al. Genetic variations of gpx-4 and male infertility in humans. Biol Reprod 2003; 68(4):1134–1141.CrossRefPubMedGoogle Scholar
  55. 55.
    Diaconu M, Tangat Y, Bohm D et al. Failure of phospholipid hydroperoxide glutathione peroxidase expression in oligoasthenozoospermia and mutations in the PHGPx gene. Andrologia 2006; 38(4):152–157.CrossRefPubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  1. 1.Department of Histology and Medical Embryology“Sapienza” University of RomeRomeItaly

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