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Antioxidants and sperm DNA damage: a clinical perspective

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Abstract

Purpose

Infertile men possess substantially more sperm DNA damage than do fertile men, damage that may impact negatively on reproductive outcomes. In this era of assisted reproductive technologies there is mounting concern regarding the safety of utilizing DNA-damaged spermatozoa in this setting. Therefore, it is important to identify strategies that may reduce sperm DNA damage. The purpose of this review is to discuss the rationale for antioxidant therapy in men with sperm DNA damage and to evaluate the data on the efficacy of dietary and in vitro antioxidant preparations on sperm DNA damage.

Methods

We reviewed the literature on antioxidants and sperm DNA damage.

Results

To date, the data suggest that dietary antioxidants may be beneficial in reducing sperm DNA damage, particularly, in men with high levels of DNA fragmentation. However, the mechanism of action of dietary antioxidants has not been established and most of the clinical studies are small. A beneficial effect of in vitro antioxidant supplements in protecting sperm DNA from exogenous oxidants has been demonstrated, however, the effect of these antioxidants in protecting sperm from endogenous ROS, gentle sperm processing and cryopreservation has not been established.

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References

  1. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008;23:2663–8.

    Article  CAS  PubMed  Google Scholar 

  2. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22:174–9.

    Article  CAS  PubMed  Google Scholar 

  3. Sigman M, Zini A. Semen analysis and sperm function assays: what do they mean? Semin Reprod Med. 2009;27:115–23.

    Article  PubMed  Google Scholar 

  4. Collins JA, Barnhart KT, Schlegel PN. Do sperm DNA integrity tests predict pregnancy with in vitro fertilization? Fertil Steril. 2008;89:823–31.

    Article  PubMed  Google Scholar 

  5. Fernandez-Gonzalez R, Moreira PN, Perez-Crespo M, Sanchez-Martin M, Ramirez MA, Pericuesta E, et al. Long-term effects of mouse intracytoplasmic sperm injection with DNA-fragmented sperm on health and behavior of adult offspring. Biol Reprod. 2008;78:761–72.

    Article  CAS  PubMed  Google Scholar 

  6. Fraga CG, Motchnik PA, Shigenaga MK, Helbock HJ, Jacob RA, Ames BN. Ascorbic acid protects against endogenous oxidative DNA damage in human sperm. Proc Natl Acad Sci U S A. 1991;88:11003–6.

    Article  CAS  PubMed  Google Scholar 

  7. Zini A, Blumenfeld A, Libman J, Willis J. Beneficial effect of microsurgical varicocelectomy on human sperm DNA integrity. Hum Reprod. 2005;20:1018–21.

    Article  CAS  PubMed  Google Scholar 

  8. Ochsendorf FR. Infections in the male genital tract and reactive oxygen species. Hum Reprod Update. 1999;5:399–420.

    Article  CAS  PubMed  Google Scholar 

  9. Sakkas D, Seli E, Bizzaro D, Tarozzi N, Manicardi GC. Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodelling during spermatogenesis. Reprod Biomed Online. 2003;7:428–32.

    PubMed  Google Scholar 

  10. Aitken RJ, De Iuliis GN, McLachlan RI. Biological and clinical significance of DNA damage in the male germ line. Int J Androl. 2009;32:46–56.

    Article  CAS  PubMed  Google Scholar 

  11. Carrell DT, Liu L. Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl. 2001;22:604–10.

    CAS  PubMed  Google Scholar 

  12. de Yebra L, Ballesca JL, Vanrell JA, Bassas L, Oliva R. Complete selective absence of protamine P2 in humans. J Biol Chem. 1993;268:10553–7.

    PubMed  Google Scholar 

  13. Iwasaki A, Gagnon C. Formation of reactive oxygen species in spermatozoa of infertile patients. Fertil Steril. 1992;57:409–16.

    CAS  PubMed  Google Scholar 

  14. Zini A, de Lamirande E, Gagnon C. Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa. Int J Androl. 1993;16:183–8.

    Article  CAS  PubMed  Google Scholar 

  15. Irvine DS, Twigg JP, Gordon EL, Fulton N, Milne PA, Aitken RJ. DNA integrity in human spermatozoa: relationships with semen quality. J Androl. 2000;21:33–44.

    CAS  PubMed  Google Scholar 

  16. Barroso G, Morshedi M, Oehninger S. Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod. 2000;15:1338–44.

    Article  CAS  PubMed  Google Scholar 

  17. Saleh RA, Agarwal A, Sharma RK, Said TM, Sikka SC, Thomas AJ Jr. Evaluation of nuclear DNA damage in spermatozoa from infertile men with varicocele. Fertil Steril. 2003;80:1431–6.

    Article  PubMed  Google Scholar 

  18. Shen HM, Chia SE, Ong CN. Evaluation of oxidative DNA damage in human sperm and its association with male infertility. J Androl. 1999;20:718–23.

    CAS  PubMed  Google Scholar 

  19. Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patients. Fertil Steril. 1997;68:519–24.

    Article  CAS  PubMed  Google Scholar 

  20. Sati L, Ovari L, Bennett D, Simon SD, Demir R, Huszar G. Double probing of human spermatozoa for persistent histones, surplus cytoplasm, apoptosis and DNA fragmentation. Reprod Biomed Online. 2008;16:570–9.

    PubMed  Google Scholar 

  21. Muratori M, Piomboni P, Baldi E, Filimberti E, Pecchioli P, Moretti E, et al. Functional and ultrastructural features of DNA-fragmented human sperm. J Androl. 2000;21:903–12.

    CAS  PubMed  Google Scholar 

  22. Gomez E, Buckingham DW, Brindle J, Lanzafame F, Irvine DS, Aitken RJ. Development of an image analysis system to monitor the retention of residual cytoplasm by human spermatozoa: correlation with biochemical markers of the cytoplasmic space, oxidative stress, and sperm function. J Androl. 1996;17:276–87.

    CAS  PubMed  Google Scholar 

  23. Aitken J, Fisher H. Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. Bioessays. 1994;16:259–67.

    Article  CAS  PubMed  Google Scholar 

  24. Alvarez JG, Touchstone JC, Blasco L, Storey BT. Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa. Superoxide dismutase as major enzyme protectant against oxygen toxicity. J Androl. 1987;8:338–48.

    CAS  PubMed  Google Scholar 

  25. Twigg J, Fulton N, Gomez E, Irvine DS, Aitken RJ. Analysis of the impact of intracellular reactive oxygen species generation on the structural and functional integrity of human spermatozoa: lipid peroxidation, DNA fragmentation and effectiveness of antioxidants. Hum Reprod. 1998;13:1429–36.

    Article  CAS  PubMed  Google Scholar 

  26. Aitken RJ, Gordon E, Harkiss D, Twigg JP, Milne P, Jennings Z, et al. Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod. 1998;59:1037–46.

    Article  CAS  PubMed  Google Scholar 

  27. Sawyer DE, Mercer BG, Wiklendt AM, Aitken RJ. Quantitative analysis of gene-specific DNA damage in human spermatozoa. Mutat Res. 2003;529:21–34.

    CAS  PubMed  Google Scholar 

  28. Jeulin C, Soufir JC, Weber P, Laval-Martin D, Calvayrac R. Catalase activity in human spermatozoa and seminal plasma. Gamete Res. 1989;24:185–96.

    Article  CAS  PubMed  Google Scholar 

  29. Gagnon C, Iwasaki A, De Lamirande E, Kovalski N. Reactive oxygen species and human spermatozoa. Ann N Y Acad Sci. 1991;637:436–44.

    Article  CAS  PubMed  Google Scholar 

  30. Zini A, Schlegel PN. Catalase mRNA expression in the male rat reproductive tract. J Androl. 1996;17:473–80.

    CAS  PubMed  Google Scholar 

  31. Zini A, Schlegel PN. Expression of glutathione peroxidases in the adult male rat reproductive tract. Fertil Steril. 1997;68:689–95.

    Article  CAS  PubMed  Google Scholar 

  32. Jow WW, Schlegel PN, Cichon Z, Phillips D, Goldstein M, Bardin CW. Identification and localization of copper-zinc superoxide dismutase gene expression in rat testicular development. J Androl. 1993;14:439–47.

    CAS  PubMed  Google Scholar 

  33. Zini A, Schlegel PN. Identification and characterization of antioxidant enzyme mRNAs in the rat epididymis. Int J Androl. 1997;20:86–91.

    Article  CAS  PubMed  Google Scholar 

  34. Sanocka D, Miesel R, Jedrzejczak P, Chelmonska-Soyta AC, Kurpisz M. Effect of reactive oxygen species and the activity of antioxidant systems on human semen; association with male infertility. Int J Androl. 1997;20:255–64.

    Article  CAS  PubMed  Google Scholar 

  35. Holmes RP, Goodman HO, Shihabi ZK, Jarow JP. The taurine and hypotaurine content of human semen. J Androl. 1992;13:289–92.

    CAS  PubMed  Google Scholar 

  36. Song GJ, Lewis V. Mitochondrial DNA integrity and copy number in sperm from infertile men. Fertil Steril. 2008;90:2238–44.

    Article  CAS  PubMed  Google Scholar 

  37. Appasamy M, Muttukrishna S, Pizzey AR, Ozturk O, Groome NP, Serhal P, et al. Relationship between male reproductive hormones, sperm DNA damage and markers of oxidative stress in infertility. Reprod Biomed Online. 2007;14:159–65.

    CAS  PubMed  Google Scholar 

  38. Verit FF, Verit A, Kocyigit A, Ciftci H, Celik H, Koksal M. No increase in sperm DNA damage and seminal oxidative stress in patients with idiopathic infertility. Arch Gynecol Obstet. 2006;274:339–44.

    Article  CAS  PubMed  Google Scholar 

  39. Xu DX, Shen HM, Zhu QX, Chua L, Wang QN, Chia SE, et al. The associations among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. Mutat Res. 2003;534:155–63.

    CAS  PubMed  Google Scholar 

  40. Lewis SE, Boyle PM, McKinney KA, Young IS, Thompson W. Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril. 1995;64:868–70.

    CAS  PubMed  Google Scholar 

  41. Smith R, Vantman D, Ponce J, Escobar J, Lissi E. Total antioxidant capacity of human seminal plasma. Hum Reprod. 1996;11:1655–60.

    CAS  PubMed  Google Scholar 

  42. Sanocka D, Miesel R, Jedrzejczak P, Kurpisz MK. Oxidative stress and male infertility. J Androl. 1996;17:449–54.

    CAS  PubMed  Google Scholar 

  43. Silver EW, Eskenazi B, Evenson DP, Block G, Young S, Wyrobek AJ. Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men. J Androl. 2005;26:550–6.

    Article  CAS  PubMed  Google Scholar 

  44. Hampl JS, Taylor CA, Johnston CS. Vitamin C deficiency and depletion in the United States: the Third National Health and Nutrition Examination Survey, 1988 to 1994. Am J Public Health. 2004;94:870–5.

    Article  PubMed  Google Scholar 

  45. Jacob RA. Assessment of human vitamin C status. J Nutr. 1990;120(Suppl 11):1480–5.

    CAS  PubMed  Google Scholar 

  46. Ryle PR, Thomson AD. Nutrition and vitamins in alcoholism. Contemp Issues Clin Biochem. 1984;1:188–224.

    CAS  PubMed  Google Scholar 

  47. Greco E, Romano S, Iacobelli M, Ferrero S, Baroni E, Minasi MG, et al. ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment. Hum Reprod. 2005;20:2590–4.

    Article  CAS  PubMed  Google Scholar 

  48. Greco E, Iacobelli M, Rienzi L, Ubaldi F, Ferrero S, Tesarik J. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26:349–53.

    Article  CAS  PubMed  Google Scholar 

  49. Menezo YJ, Hazout A, Panteix G, Robert F, Rollet J, Cohen-Bacrie P, et al. Antioxidants to reduce sperm DNA fragmentation: an unexpected adverse effect. Reprod Biomed Online. 2007;14:418–21.

    Article  CAS  PubMed  Google Scholar 

  50. Tremellen K, Miari G, Froiland D, Thompson J. A randomised control trial examining the effect of an antioxidant (Menevit) on pregnancy outcome during IVF-ICSI treatment. Aust N Z J Obstet Gynaecol. 2007;47:216–21.

    Article  PubMed  Google Scholar 

  51. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A. Role of male factor in early recurrent embryo loss: do antioxidants have any effect? Fertil Steril 2008.

  52. Piomboni P, Gambera L, Serafini F, Campanella G, Morgante G, De Leo V. Sperm quality improvement after natural anti-oxidant treatment of asthenoteratospermic men with leukocytospermia. Asian J Androl. 2008;10:201–6.

    Article  PubMed  Google Scholar 

  53. Twigg J, Irvine DS, Houston P, Fulton N, Michael L, Aitken RJ. Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma. Mol Hum Reprod. 1998;4:439–45.

    Article  CAS  PubMed  Google Scholar 

  54. Said TM, Agarwal A, Sharma RK, Thomas AJ Jr, Sikka SC. Impact of sperm morphology on DNA damage caused by oxidative stress induced by beta-nicotinamide adenine dinucleotide phosphate. Fertil Steril. 2005;83:95–103.

    Article  CAS  PubMed  Google Scholar 

  55. Lopes S, Jurisicova A, Sun JG, Casper RF. Reactive oxygen species: potential cause for DNA fragmentation in human spermatozoa. Hum Reprod. 1998;13:896–900.

    Article  CAS  PubMed  Google Scholar 

  56. Potts RJ, Notarianni LJ, Jefferies TM. Seminal plasma reduces exogenous oxidative damage to human sperm, determined by the measurement of DNA strand breaks and lipid peroxidation. Mutat Res. 2000;447:249–56.

    CAS  PubMed  Google Scholar 

  57. Sierens J, Hartley JA, Campbell MJ, Leathem AJ, Woodside JV. In vitro isoflavone supplementation reduces hydrogen peroxide-induced DNA damage in sperm. Teratog Carcinog Mutagen. 2002;22:227–34.

    Article  CAS  PubMed  Google Scholar 

  58. Russo A, Troncoso N, Sanchez F, Garbarino JA, Vanella A. Propolis protects human spermatozoa from DNA damage caused by benzo[a]pyrene and exogenous reactive oxygen species. Life Sci. 2006;78:1401–6.

    Article  CAS  PubMed  Google Scholar 

  59. Cemeli E, Schmid TE, Anderson D. Modulation by flavonoids of DNA damage induced by estrogen-like compounds. Environ Mol Mutagen. 2004;44:420–6.

    Article  CAS  PubMed  Google Scholar 

  60. Dobrzynska MM, Baumgartner A, Anderson D. Antioxidants modulate thyroid hormone- and noradrenaline-induced DNA damage in human sperm. Mutagenesis. 2004;19:325–30.

    Article  CAS  PubMed  Google Scholar 

  61. Anderson D, Schmid TE, Baumgartner A, Cemeli-Carratala E, Brinkworth MH, Wood JM. Oestrogenic compounds and oxidative stress (in human sperm and lymphocytes in the Comet assay). Mutat Res. 2003;544:173–8.

    Article  CAS  PubMed  Google Scholar 

  62. Chi HJ, Kim JH, Ryu CS, Lee JY, Park JS, Chung DY, et al. Protective effect of antioxidant supplementation in sperm-preparation medium against oxidative stress in human spermatozoa. Hum Reprod. 2008;23:1023–8.

    Article  CAS  PubMed  Google Scholar 

  63. Donnelly ET, McClure N, Lewis SE. The effect of ascorbate and alpha-tocopherol supplementation in vitro on DNA integrity and hydrogen peroxide-induced DNA damage in human spermatozoa. Mutagenesis. 1999;14:505–12.

    Article  CAS  PubMed  Google Scholar 

  64. Hughes CM, Lewis SE, McKelvey-Martin VJ, Thompson W. The effects of antioxidant supplementation during Percoll preparation on human sperm DNA integrity. Hum Reprod. 1998;13:1240–7.

    Article  CAS  PubMed  Google Scholar 

  65. Donnelly ET, McClure N, Lewis SE. Glutathione and hypotaurine in vitro: effects on human sperm motility, DNA integrity and production of reactive oxygen species. Mutagenesis. 2000;15:61–8.

    Article  CAS  PubMed  Google Scholar 

  66. Taylor K, Roberts P, Sanders K, Burton P. Effect of antioxidant supplementation of cryopreservation medium on post-thaw integrity of human spermatozoa. Reprod Biomed Online. 2009;18:184–9.

    Article  PubMed  Google Scholar 

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Correspondence to Armand Zini.

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Capsule Dietary and in vitro antioxidant preparations may help reduce sperm DNA damage, however, larger, well-designed studies are needed to firmly establish the utility of antioxidants in this setting.

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Zini, A., San Gabriel, M. & Baazeem, A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet 26, 427–432 (2009). https://doi.org/10.1007/s10815-009-9343-5

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  • DOI: https://doi.org/10.1007/s10815-009-9343-5

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