Advertisement

Sperm DNA Damage and Antioxidant Use: Roles in Male Fertility

  • Ashok AgarwalEmail author
  • Aspinder Singh
Chapter

Abstract

The physician and andrologist must turn to semen characteristics to decipher what are the causative agents behind male infertility. WHO standard protocol requires analysis of sperm concentration, motility, and morphology. However, recent evidence implies that such parameters are not enough to fully depict the basis for male infertility and suggests that the effects of sperm DNA damage on infertility be considered. With the increasing ease of artificial reproduction, factors effecting embryo viability and offspring health related to the quality of sperm used and associated integrity of DNA must be strictly analyzed. Male gametes with damaged DNA can transmit genetic defects, lead to pregnancy loss, infant mortality, birth defects, and genetic diseases in the offspring. Furthermore, studies report that more than 80% of the structural de novo chromosome aberrations are of paternal origin. This chapter will begin by reviewing the process of spermatozoal chromatin organization and DNA packaging. Next, DNA damage and the factors causing this damage shall be considered. Subsequently, recognition and detection of this DNA damage will be reviewed followed finally by the effects of this damage and clinical applications encompassing treatment options involving antioxidants.

Keywords

Male infertility Antioxidants Sperm DNA damage Spermatozoal chromatin organization DNAse-insensitive toroids Reactive oxygen species Florescent in situ hybridization 

References

  1. 1.
    Dunson DB, Baird DD, Colombo B. Increased infertility with age in men and women. Obstet Gynecol. 2004;103:51–6.PubMedCrossRefGoogle Scholar
  2. 2.
    World Health Organization, DoRHaR. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.Google Scholar
  3. 3.
    Marchetti F, Essers J, Kanaar R, Wyrobek AJ. Disruption of maternal DNA repair increases sperm-derived chromosomal aberrations. Proc Natl Acad Sci USA. 2007;104:17725–9.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Fernandez-Gonzalez R, Moreira PN, Perez-Crespo M, 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.PubMedCrossRefGoogle Scholar
  6. 6.
    Thomas NS, Durkie M, Van Zyl B, et al. Parental and chromosomal origin of unbalanced de novo structural chromosome abnormalities in man. Hum Genet. 2006;119:444–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Fuentes-Mascorro G, Serrano H, Rosado A. Sperm chromatin. Arch Androl. 2000;45:215–25.PubMedCrossRefGoogle Scholar
  8. 8.
    Ward WS. Function of sperm chromatin structural elements in fertilization and development. Mol Hum Reprod. 2010;16:30–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Sotolongo B, Lino E, Ward WS. Ability of hamster spermatozoa to digest their own DNA. Biol Reprod. 2003;69:2029–35.PubMedCrossRefGoogle Scholar
  10. 10.
    Mudrak O, Chandra R, Jones E, Godfrey E, Zalensky A. Reorganisation of human sperm nuclear architecture during formation of pronuclei in a model system. Reprod Fertil Dev. 2009;21:665–71.PubMedCrossRefGoogle Scholar
  11. 11.
    Martins RP, Ostermeier GC, Krawetz SA. Nuclear matrix interactions at the human protamine domain: a working model of potentiation. J Biol Chem. 2004;279:51862–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Ogura A, Matsuda J, Yanagimachi R. Birth of normal young after electrofusion of mouse oocytes with round spermatids. Proc Natl Acad Sci USA. 1994;91:7460–2.PubMedCrossRefGoogle Scholar
  13. 13.
    Ajduk A, Yamauchi Y, Ward MA. Sperm chromatin remodeling after intracytoplasmic sperm injection differs from that of in vitro fertilization. Biol Reprod. 2006;75:442–51.PubMedCrossRefGoogle Scholar
  14. 14.
    Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR. Distinctive chromatin in human sperm packages genes for embryo development. Nature. 2009;460:473–8.PubMedGoogle Scholar
  15. 15.
    Ostermeier GC, Goodrich RJ, Diamond MP, Dix DJ, Krawetz SA. Toward using stable spermatozoal RNAs for prognostic assessment of male factor fertility. Fertil Steril. 2005;83:1687–94.PubMedCrossRefGoogle Scholar
  16. 16.
    Arpanahi A, Brinkworth M, Iles D, et al. Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences. Genome Res. 2009;19:1338–49.PubMedCrossRefGoogle Scholar
  17. 17.
    van der Heijden GW, Ramos L, Baart EB, et al. Sperm-derived histones contribute to zygotic chromatin in humans. BMC Dev Biol. 2008;8:34.PubMedCrossRefGoogle Scholar
  18. 18.
    Shaman JA, Yamauchi Y, Ward WS. The sperm nuclear matrix is required for paternal DNA replication. J Cell Biochem. 2007;102:680–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Zalenskaya IA, Bradbury EM, Zalensky AO. Chromatin structure of telomere domain in human sperm. Biochem Biophys Res Commun. 2000;279:213–8.PubMedCrossRefGoogle Scholar
  20. 20.
    Churikov D, Siino J, Svetlova M, et al. Novel human testis-specific histone H2B encoded by the interrupted gene on the X chromosome. Genomics. 2004;84:745–56.PubMedCrossRefGoogle Scholar
  21. 21.
    Mudrak O, Tomilin N, Zalensky A. Chromosome architecture in the decondensing human sperm nucleus. J Cell Sci. 2005;118:4541–50.PubMedCrossRefGoogle Scholar
  22. 22.
    Zalensky A, Zalenskaya I. Organization of chromosomes in spermatozoa: an additional layer of epigenetic information? Biochem Soc Trans. 2007;35:609–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Spano M, Seli E, Bizzaro D, Manicardi GC, Sakkas D. The significance of sperm nuclear DNA strand breaks on reproductive outcome. Curr Opin Obstet Gynecol. 2005;17:255–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Menezo Y, Dale B, Cohen M. DNA damage and repair in human oocytes and embryos: a review. Zygote. 2010;18(4):357–65.PubMedCrossRefGoogle Scholar
  25. 25.
    Erenpreiss J, Spano M, Erenpreisa J, Bungum M, Giwercman A. Sperm chromatin structure and male fertility: biological and clinical aspects. Asian J Androl. 2006;8:11–29.PubMedCrossRefGoogle Scholar
  26. 26.
    Liu L, Trimarchi JR, Smith PJ, Keefe DL. Mitochondrial dysfunction leads to telomere attrition and genomic instability. Aging Cell. 2002;1:40–6.PubMedCrossRefGoogle Scholar
  27. 27.
    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.PubMedCrossRefGoogle Scholar
  28. 28.
    Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update. 2003;9:331–45.PubMedCrossRefGoogle Scholar
  29. 29.
    Padron OF, Sharma RK, Thomas Jr AJ, Agarwal A. Effects of cancer on spermatozoa quality after cryopreservation: a 12-year experience. Fertil Steril. 1997;67:326–31.PubMedCrossRefGoogle Scholar
  30. 30.
    Kasturi SS, Charles Osterberg E, Tannir J, Brannigan RE. The effect of genital tract infection and inflammation on male infertility. In: Lipshiltz LI, Howards SS, Neiderberger CS, editors. Infertility in the male. 4th ed. Cambridge: Cambridge University Press; 2009. p. 295–330.CrossRefGoogle Scholar
  31. 31.
    Aitken RJ, De Iuliis GN. On the possible origins of DNA damage in human spermatozoa. Mol Hum Reprod. 2010;16:3–13.PubMedCrossRefGoogle Scholar
  32. 32.
    Loft S, Kold-Jensen T, Hjollund NH, et al. Oxidative DNA damage in human sperm influences time to pregnancy. Hum Reprod. 2003;18:1265–72.PubMedCrossRefGoogle Scholar
  33. 33.
    Saleh RA, Agarwal A, Sharma RK, Nelson DR, Thomas Jr AJ. Effect of cigarette smoking on levels of seminal oxidative stress in infertile men: a prospective study. Fertil Steril. 2002;78:491–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Chang JS. Parental smoking and childhood leukemia. Methods Mol Biol. 2009;472:103–37.PubMedCrossRefGoogle Scholar
  35. 35.
    Sepaniak S, Forges T, Gerard H, Foliguet B, Bene MC, Monnier-Barbarino P. The influence of cigarette smoking on human sperm quality and DNA fragmentation. Toxicology. 2006;223:54–60.PubMedCrossRefGoogle Scholar
  36. 36.
    Chatterjee R, Haines GA, Perera DM, Goldstone A, Morris ID. Testicular and sperm DNA damage after treatment with fludarabine for chronic lymphocytic leukaemia. Hum Reprod. 2000;15:762–6.PubMedCrossRefGoogle Scholar
  37. 37.
    Campbell DI, Bunn JE, Weaver LT, Harding M, Coward WA, Thomas JE. Human milk vacuolating cytotoxin A immunoglobulin A antibodies modify Helicobacter pylori infection in Gambian children. Clin Infect Dis. 2006;43:1040–2.PubMedCrossRefGoogle Scholar
  38. 38.
    Younglai EV, Holt D, Brown P, Jurisicova A, Casper RF. Sperm swim-up techniques and DNA fragmentation. Hum Reprod. 2001;16:1950–3.PubMedCrossRefGoogle Scholar
  39. 39.
    Zini A, Finelli A, Phang D, Jarvi K. Influence of semen processing technique on human sperm DNA integrity. Urology. 2000;56:1081–4.PubMedCrossRefGoogle Scholar
  40. 40.
    Larson KL, Brannian JD, Timm BK, Jost LK, Evenson DP. Density gradient centrifugation and glass wool filtration of semen remove spermatozoa with damaged chromatin structure. Hum Reprod. 1999;14:2015–9.PubMedCrossRefGoogle Scholar
  41. 41.
    Hamatani T, Falco G, Carter MG, et al. Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet. 2004;13:2263–78.PubMedCrossRefGoogle Scholar
  42. 42.
    Yamagata K, Suetsugu R, Wakayama T. Assessment of chromosomal integrity using a novel live-cell imaging technique in mouse embryos produced by intracytoplasmic sperm injection. Hum Reprod. 2009;24:2490–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Kimura Y, Yanagimachi R. Mouse oocytes injected with testicular spermatozoa or round spermatids can develop into normal offspring. Development. 1995;121:2397–405.PubMedGoogle Scholar
  44. 44.
    Duran EH, Morshedi M, Taylor S, Oehninger S. Sperm DNA quality predicts intrauterine insemination outcome: a prospective cohort study. Hum Reprod. 2002;17:3122–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Bungum M, Humaidan P, Axmon A, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22:174–9.PubMedCrossRefGoogle Scholar
  46. 46.
    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.PubMedCrossRefGoogle Scholar
  47. 47.
    Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004;81:1289–95.PubMedCrossRefGoogle Scholar
  48. 48.
    Aitken RJ, Krausz C. Oxidative stress, DNA damage and the Y chromosome. Reproduction. 2001;122:497–506.PubMedCrossRefGoogle Scholar
  49. 49.
    Fagerstedt K, Blokhina O. Oxidative stress and antioxidant defences in plants. In: Singh KK, editor. Oxidative stress, disease and cancer. London: Imperial College Press; 2006. p. 151–99.Google Scholar
  50. 50.
    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 USA. 1991;88:11003–6.PubMedCrossRefGoogle Scholar
  51. 51.
    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.PubMedCrossRefGoogle Scholar
  52. 52.
    Zini A, San Gabriel M, Baazeem A. Antioxidants and sperm DNA damage: a clinical perspective. J Assist Reprod Genet. 2009;26:427–32.PubMedCrossRefGoogle Scholar
  53. 53.
    Boxmeer JC, Smit M, Utomo E, et al. Low folate in seminal plasma is associated with increased sperm DNA damage. Fertil Steril. 2009;92:548–56.PubMedCrossRefGoogle Scholar
  54. 54.
    Zini A, San Gabriel M, Libman J. Lycopene supplementation in vitro can protect human sperm deoxyribonucleic acid from oxidative damage. Fertil Steril. 2010;94:1033–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Barratt CL, De Jonge CJ. Clinical relevance of sperm DNA assessment: an update. Fertil Steril. 2010;94(6):1958–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Center for Reproductive Medicine, Glickman Urological and Kidney InstituteCleveland Clinic FoundationClevelandUSA

Personalised recommendations