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Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction

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Abstract

The excessive generation of reactive oxygen species (ROS) by abnormal spermatozoa and contaminating leukocytes has been defined as one of the few etiologies for male infertility. Administration of antioxidants in patients with ‘male factor’ infertility has begun to attract considerable interest. The main difficulty of such an approach is our incomplete understanding of the role of free radicals in normal and abnormal sperm function leading to male infertility. Mammalian spermatozoa membranes are very sensitive to free radical induced damage mediated by lipid peroxidation, as they are rich in polyunsaturated fatty acids. Limited endogenous mechanisms exist to reverse these damages. ROS attacks the fluidity of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. ROS induced DNA damage accelerate the germ cell apoptosis. Unfortunately spermatozoa are unable to repair the damage induced by excessive ROS as they lack the cytoplasmic enzymes required to accomplish the repair. Assessment of such oxidative stress status (OSS) may help in the medical treatment. Treatment strategies must be directed toward lowering of ROS levels to keep only a small amount necessary to maintain normal cell function.

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References

  1. Hull, M., Glazener, C., Kelly, N., Conway, D., Foster, P., Hunton, R., Coulson, C., Lambert, P., Watt, E. and Desai, K. (1985) Population study of causes, treatment and outcome of infertility. Br Med J. 291, 1693–1697.

    Article  CAS  Google Scholar 

  2. Maneesh, M., Jayalekshmi, H., Dutta, S., Chakrabarti, A. and Vasudevan, D. M. (2005) Effect of chronic ethanol administration on testicular antioxidant system and steroidogenic enzymes in rats. Ind. J. of Exp. Biol. 43, 445–449.

    CAS  Google Scholar 

  3. Maneesh, M., Jayalekshmi, H., Singh, T. A. and Chakrabarti, A. (2006) Impaired hypothalamic pituitary gonadal axis function in men with diabetes mellitus. Ind. J. of Clin. Biochem. 21 (1), 165–168.

    Article  CAS  Google Scholar 

  4. Koppenol, W., Moreno, J., Pryor, W., Ischiropoulos, H. & Beckman J. S. (1992) Peroxynitrite, a cloaked oxidant formed by nitric oxide and superoxide. Chemical Res. in Toxicol. 5, 834–842.

    Article  CAS  Google Scholar 

  5. Sikka, S. C. (1996) Oxidative stress and role of antioxidants in normal and abnormal sperm function. Front. Biosci. 1, 78–86.

    Google Scholar 

  6. Alvarez J. G. and Storey, B. T. (1995) Differential incorporation of fatty acids into and peroxidative loss of fatty acids from phospholipids of human spermatozoa. Mol. Reprod. Dev. 42, 334–346.

    Article  PubMed  CAS  Google Scholar 

  7. Armstrong, J. S., Rajasekaran, M., Hellstrom, W. J. and Sikka, S. C. (1998) Antioxidant potential of human serum albumin: role in the recovery of high quality human spermatozoa for assisted reproductive technology. J. Androl. 19, 412–419.

    PubMed  CAS  Google Scholar 

  8. Alvarez, J. G., Touchstone, J. C., Blasco, L. and Storey, B. T. (1987) Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J. Androl. 8, 338–348.

    PubMed  CAS  Google Scholar 

  9. Aitken, R. J., Paterson, M., Fisher, H., Buckingham, D. W. and van Duin, M. (1995) Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J. Cell. Sci. 8, 2017–2025.

    Google Scholar 

  10. Calvin, H. I., Cooper, G. W. and Wallace, E. W. (1981) Evidence that selenium in rat sperm is associated with a cysteine rich structural proteins of the mitochondrial capsule. Gamete Res. 4, 139–145

    Article  CAS  Google Scholar 

  11. Lenzi, A., Picardo, M., Gandini, L., Lombardo, F., Terminali, O., Passi, S. and Dondero, F. (1994) Glutathione treatment of dyspermia: effect on the lipoperoxidation process. Hum. Reprod. 9, 2044–2050

    PubMed  CAS  Google Scholar 

  12. Irvine, D. S. (1996) Glutathione as a treatment for male infertility. Reviews of Reprod. 1, 6–12

    Article  CAS  Google Scholar 

  13. Wefers, H. and Sies, H (1988) The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. Eur J Biochem. 174, 353–357.

    Article  PubMed  CAS  Google Scholar 

  14. Maneesh, M., Jayalekshmi, H., Dutta, S., Chakrabarti, A. and Vasudevan, D. M. (2005) Experimental therapeutical intervention with ascorbic acid in ethanol induced testicular injuries in rats. Ind. J. of Exp. Biol. 43, 172–176.

    CAS  Google Scholar 

  15. Buettner, G. R. (1993) The pecking order of free radicals and antioxidants, lipid peroxidation, alpha-tocopherol and ascorbate. Arch. Biochem. Biophys. 300, 535–543.

    Article  PubMed  CAS  Google Scholar 

  16. Sies, H. (1993) Strategies of antioxidant defence. Eur. J. Biochem. 215, 213–219.

    Article  PubMed  CAS  Google Scholar 

  17. Iwasaki, A. and Gagnon, C. (1992) Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil. Steril. 57, 409–416.

    PubMed  CAS  Google Scholar 

  18. Sikka, S. C., Rajasekaran, M. and Hellstrom, H. J. (1995) Role of oxidative stress and antioxidants in male infertility. J. Androl. 16, 464–468.

    PubMed  CAS  Google Scholar 

  19. Joyce, D. A. (1987) Oxygen radicals in disease. Adverse Drug Reaction Bull. 127, 476–479.

    Article  Google Scholar 

  20. Sharma, R. K. and Agarwal, A. (1996) Role of reactive oxygen species in male infertility [review]. Urology. 48, 835–850.

    Article  PubMed  CAS  Google Scholar 

  21. Rajasekaran, M., Hellstrom, W. J. and Sikka, S. C. (1996) Quantitative assessment of cytokines (GRO-a and IL-10) in human seminal plasma during genitourinary inflammation. Am. J. Reprod. Immun. 36.

  22. Thomas, J., Fishel, S. B., Hall, J. A., Green, S., Newton, T. A. and Thornton, S. J. (1997) Increased polymorphonuclear granulocytes in seminal plasma in relation to sperm morphology. Hum. Reprod. 12, 2418–2421.

    Article  PubMed  CAS  Google Scholar 

  23. Wolff, H. (1995) The biologic significance of white blood cells in semen. Fertil. Steril. 63, 1143–1147.

    PubMed  CAS  Google Scholar 

  24. Tomlinson, M. J., Barrat, G. L. R. and Cooke, I. D. (1993) Prospective study of leukocytes and leukocyte subpopulations in semen suggests that they are not a cause of male infertility. Fertil. Steril. 60, 1069–1075.

    PubMed  CAS  Google Scholar 

  25. Kessopoulou, E., Tomlinson, M. J., Barratt, C. L., Bolton, A. E. and Cooke, I. D. (1992) Origin of reactive oxygen species in human semen: spermatozoa or leucocytes? J. Reprod. Fertil. 94, 463–470.

    PubMed  CAS  Google Scholar 

  26. Krausz, C., Mills, C., Rogers, S., Tan, S. L. and Aitken, R. J. (1994) Stimulation of oxidant generation by human sperm suspensions using phorbol esters and formyl peptides: relationships with motility and fertilizationin vitro. Fertil. Steril. 62, 599–605.

    PubMed  CAS  Google Scholar 

  27. Iwasaki, A. and Gagnon, C. (1992) Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil. Steril. 57, 409–416.

    PubMed  CAS  Google Scholar 

  28. Aitken, R. J. and Clarkson, J. S. (1987) Cellular basis of defective sperm function and its association with the genesis of reactive oxygen species by human spermatozoa. J. Reprod. Fertil. 81, 459–469.

    PubMed  CAS  Google Scholar 

  29. Ollero, M., Gil-Guzman, E., Lopez, M. C., Sharma, R. K., Agarwal, A. and Larson, K. L. (2001) Characterization of subsets of human spermatozoa at different stages of maturation: implications in the diagnosis and treatment of male infertility. Hum. Reprod. 16, 1912–1921.

    Article  PubMed  CAS  Google Scholar 

  30. Gil-Guzman, E., Ollero, M., Lopez, M. C., Sharma, R. K., Alvarez, J. G. and Thomas, A. J. Jr. (2001) Differential production of reactive oxygen species by subsets of human spermatozoa at different stages of maturation. Hum. Reprod. 16, 1922–1930.

    Article  PubMed  CAS  Google Scholar 

  31. World Health Organization. Laboratory manual for the examination of human semen and sperm-cevical mucus interaction. 4th ed. New York. Cambridge University Press, 1999.

    Google Scholar 

  32. Kruger, T. F., Acosta, A. A., Simmons, K. F., Swanson, R. J., Matta, J. F. and Weeck, L. L. (1987) New method of evaluating sperm morphology with predictive value for human in vitro fertilization. Urology 30, 248–251.

    Article  PubMed  CAS  Google Scholar 

  33. Agarwal, A., Ikemoto, I. and Loughlin, K. R. (1992) Levels of reactive oxygen species before and after sperm preparation: comparison of swim-up and L4 filtration methods. Arch. Androl. 32, 169–174.

    Article  Google Scholar 

  34. Agarwal, A., Ikemoto, I. and Loughlin, K. R. (1994) Effect of sperm washing on reactive oxygen species level in semen. Arch. Androl. 33, 157–162.

    Article  PubMed  CAS  Google Scholar 

  35. Shekarriz, M., Thomas, A. J. Jr. and Agarwal, A. (1995) A method of human semen centrifugation to minimize the iatrogenic sperm injuries caused by reactive oxygen species. Eur. Urol. 28, 31–35.

    PubMed  CAS  Google Scholar 

  36. Lopes, S., Jurisicova, A., Sun, J. and Casper, R. F. (1998) Reactive oxygen species: a potential cause for DNA fragmentation in human spermatozoa. Hum. Reprod. 13, 896–900.

    Article  PubMed  CAS  Google Scholar 

  37. Zini, A., Finelli, A., Phang, D. and Jarvi, K. (2000) Influence of semen processing on human sperm DNA integrity. Urology 56, 1081–1084.

    Article  PubMed  CAS  Google Scholar 

  38. Aitken, R. J., Krausz, C. and Buckingham, D. (1994) Relationship between biochemical markers for residual sperm cytoplasm, reactive oxygen species generation and the presence of leukocytes and precursor germ cells in human sperm suspension. Mol. Reprod. Dev. 39, 268–279.

    Article  PubMed  CAS  Google Scholar 

  39. Rajasekaran, M., Hellstrom, W. J., Naz, R. K. and Sikka, S. C. (1995) Oxidative stress and interleukins in seminal plasma during leukocytospermia. Fertil. Steril. 64, 166–171.

    PubMed  CAS  Google Scholar 

  40. Shekarriz, M., Sharma, R. K., Thomas, A. J. Jr. and Agarwal, A. (1995) Positive myeloperoxidase staining (Endtz Test) as an indicator of excessive reactive oxygen species formation in semen. J. Assist. Reprod. Genet. 12, 70–74.

    Article  PubMed  CAS  Google Scholar 

  41. Pasqualotto, F. F., Sharma, R. K., Agarwal, A., Nelson, D. R., Thomas, A. J. Jr, and Potts, J. M. (2000) Seminal oxidative stress in chronic prostatitis patients. Urology 55, 881–885.

    Article  PubMed  CAS  Google Scholar 

  42. Saran, M., Beck-Speier, I., Fellerhoff, B. and Bauer, G. (1999) Phagocytic killing of microorganisms by radical processes: consequences of the reaction of hydroxyl radicals with chloride yielding chlorine atoms. Free Radic. Biol. Med. 26, 482–490.

    Article  PubMed  CAS  Google Scholar 

  43. Ochsendorf, F. R. (1999) Infections in the male genital tract and reactive oxygen species. Hum. Reprod. 5, 399–420.

    Article  CAS  Google Scholar 

  44. Sharma, R., Pasqualotto, F. F., Nelson, D. R., Thomas, A. J. Jr and Agarwal, A. (2001) Relationship between seminal white blood cell counts and oxidative stress in men treated at an infertility clinic. J. Androl. 22, 575–583.

    PubMed  CAS  Google Scholar 

  45. Kovalski, N. N., de Lamirande, E. and Gagnon, C. (1992) Reactive oxygen species generated by human neutrophils inhibit sperm motility: protective effects of seminal plasma and scavengers. Fertil. Steril. 58, 809–816.

    PubMed  CAS  Google Scholar 

  46. Saleh, R. A., Agarwal, A., Kandirali, E., Sharma, R. K., Thomas, A. J. Jr and Nada, E. A. (2002) Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil. Steril. 78, 1215–1224.

    Article  PubMed  Google Scholar 

  47. Spitteler, G. (1993) Review: on the chemistry of oxidative stress. J. Lipid Mediat. 7, 77–82.

    Google Scholar 

  48. Jannsen, Y. M., Van-Houton, B., Borm, P. J. and Mossuran, B. T. (1993) Cell and tissue responses to oxidative damage. Lab. Invest. 69, 261–265.

    Google Scholar 

  49. de Lamirande, E., Jiang, H., Zini, A., Kodoma, H. and Gagnon, C. (1997). Reactive oxygen species (ROS) and sperm physiology. Rev. Reprod. 2, 48–54.

    Article  PubMed  Google Scholar 

  50. Sikka, S. C., Rajasekaran, M. and Hellstrom, W. J. G. (1995) Role of oxidative stress and antioxidants in male-infertility. J. Androl. 16, 464–468.

    PubMed  CAS  Google Scholar 

  51. Halliwell, b. (1990) How to characterize a biological antioxidant. Free Radic. Res. Commun. 9, 1–32.

    Article  PubMed  CAS  Google Scholar 

  52. Aitken, R. J. and Fisher, H. (1994) Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. Bioassays 16, 259–267.

    Article  CAS  Google Scholar 

  53. Lenzi, A., Cualosso, F., Gandini, L., Lombardo, F. and Dondero, F. (1993) Placebo controlled, double-blind, cross-over trial of glutathione therapy, in male infertility. Hum. Reprod. 9, 2044–2050.

    Google Scholar 

  54. Agarwal, A., Ikemoto, I. and Loughlin, K. R. (1994) Relationship of sperm parameters to levels of reactive oxygen species in semen specimens. J. Urol. 152, 107–110.

    PubMed  CAS  Google Scholar 

  55. Ernster, L. Lipid peroxidation in biological membranes: mechanisms and implications. In: Active oxygen, lipid peroxides and antioxidants. Ed: Yagi K, CRC Press, Boca Raton, 1–38 (1993)

    Google Scholar 

  56. Darley-Usmar, V., Wiseman, H. and Halliwell, B. (1995) Nitric oxide and oxygen radicals: a question of balance. FEBS Letters 369, 131–135.

    Article  PubMed  CAS  Google Scholar 

  57. Taourel, D. B., Guerin, M. C. and Torreilles, J. (1992) Is melonaldehyde a valuable indicator of lipid peroxidation? Biochem. Pharmacol. 44, 985–988.

    Article  Google Scholar 

  58. Armstrong, I. S., Rajasekaran, M., Chamulitrat, W., Gatti, P., Hellstrom, W. J. and Sikka, S. C. (1999) Characterization of reactive oxygen species induced effects on human spermatozoa movement and energy metabolism. Free Radic. Biol. Med. 26, 869–880.

    Article  PubMed  CAS  Google Scholar 

  59. de Lamirande, E. and Gagnon, C. (1995) Impact of reactive oxygen species on spermatozoa: a balancing act between beneficial and detrimental effects. Hum. Reprod. 10, 15–21.

    PubMed  CAS  Google Scholar 

  60. Aitken, R. J. (1997) Molecular mechanisms regulating human sperm functions. Mol. Hum. Reprod. 3, 169–173.

    Article  PubMed  CAS  Google Scholar 

  61. Grivaeu, J. F., Dumont, E., Renard, B., Callegari, J. P. and Lannou, D. L. (1995) Reactive oxygen species, lipid peroxidation and enzymatic defense systems in human spermatozoa. J. Reprod. Fertil. 103, 17–26.

    Article  Google Scholar 

  62. Twigg, J., Irvine, D. S. and Aitken, R. J. (1998) Oxidative damage to DNA in human spermatozoa does not, preclude pronucleous formation at intracytoplamic sperm injection. Hum. Reprod. 13, 1864–1871.

    Article  PubMed  CAS  Google Scholar 

  63. Duru, N. K., Morshedi, M. and Ochninger, S. (2000) Effects of hydrogen peroxide on DNA and plasma membrane integrity of human spermatozoa. Fertil. Steril. 74, 1200–1207.

    Article  Google Scholar 

  64. Aitken, R. J. and Krausz, C. (2001) Oxidative stress, DNA damage and the Y chromosome. Reproduction 122, 497–506.

    Article  PubMed  CAS  Google Scholar 

  65. Aitken, R. J., West, K. M. and Buckingham, D. W. (1994) Leoukocyte infiltration into the human ejaculate and its association with semen quality, oxidative stress, and sperm function. J. Androl. 15, 343–352.

    PubMed  CAS  Google Scholar 

  66. Fraga, G. G., Motchnik, P. A., Shigenaga, M. K., Helbrock, J. H., Jacob, R. A. and Ames (1991) Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc. Natl. Acad. Sci. USA 88, 11003–11006.

    Article  PubMed  CAS  Google Scholar 

  67. Sun, J. G., Jurisicova, A. and Casoer, R. F. (1997) Detection of deoxyribonucleic acid fragmentation human sperm: correlation with fertilization in vitro. Biol. Reprod 56, 519–524.

    Article  Google Scholar 

  68. Cummins, J. M., Jequier, A. M. and Raymons, K. (1994) Molecular biology of human male infertility: links with aging, mitochondrial genetics, and oxidative stress? Mol Rep and Dev 37, 345–362.

    Article  CAS  Google Scholar 

  69. Aitken, R. J. and Baker, M. A. (2003) Oxidative stress and male reproductive biology. Reproduction, Fertility and development 16 (5), 581–588.

    Article  Google Scholar 

  70. Sentman, C. L., Shutter, J. R., Hockenbery, D., Kanagawa, O. and Korsmeyer, S. J. (1991) Bcl-2 inhibits multiple forms of apoptosis but not negative selection in thyocytes. Cell 67, 879–888.

    Article  PubMed  CAS  Google Scholar 

  71. Maneesh, M., Jayalekshmi, H., Dutta, S., Chakrabarti, A. and Vasudevan, D. M. (2005) Role of oxidative stress in ethanol induced germ cell apoptosis—an experimental study in rats. Ind. J. of Clin. Biochem. 20 (2), 62–67.

    Article  CAS  Google Scholar 

  72. Lee, J., Richburg, J. H., Yonkin, S. C. and Bockelheide, K. (1997) The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology 138, 2081–2088.

    Article  PubMed  CAS  Google Scholar 

  73. Kane, D. J., Sarafian, T. A., Anton, R., Hahn, H., Gralla, E. B. and Valentine, J. S. (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274–1277.

    Article  PubMed  CAS  Google Scholar 

  74. Bar-Chama, N. and Lamb, D. (1994) Evaluation of sperm function. What is available in the modern andrology laboratory? Urologic Clinics of North Am. 21, 433–446.

    CAS  Google Scholar 

  75. Gagnon, C., Iwasaki, A., de Lamirande, E. and Kovalski, N. (1991) Reactive oxygen species and human spermatozoa. Ann NY Acad Sci 637, 436–444.

    Article  PubMed  CAS  Google Scholar 

  76. Rajasekaran, M., Hellstrom, W. J., Naz, R. K. and Sikka, S. C. (1995) Oxidative stress and interleukins in seminal plasma during leukocytospermia. Fertil. Steril. 64, 166–171.

    PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry, Melaka Manipal Medical College, 576 104, Manipal

    M Maneesh

  2. Sikkim Manipal Institute of Medical Sciences, 737102, Gangtok

    H Jayalekshmi

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Maneesh, M., Jayalekshmi, H. Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction. Indian J Clin Biochem 21, 80–89 (2006). https://doi.org/10.1007/BF02912918

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