Abstract
Due to its particular “silent” metabolic state, without transcription or translation, and a low level of cytosolic protective activities, mature sperm is a cellular type of aerobic organisms particularly at risk of oxidative damage. Despite the efforts of the male genital tract to treat this problem, a subcellular compartment of the sperm, the nucleus, and consequently, the paternal DNA cannot be effectively protected. There is an accumulation of evidence that oxidative damage to sperm DNA is quite common in male infertilities/subfertilities with potential harmful impacts on reproductive success, including the transgenerational inheritance of a paternal chromosomal lot carrying mutations.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aitken RJ (1997) Molecular mechanisms regulating human sperm function. Mol Hum Reprod 3(3):169–173
Aitken RJ (2011) The capacitation-apoptosis highway: oxysterols and mammalian sperm function. Biol Reprod 85(1):9–12. https://doi.org/10.1095/biolreprod.111.092528
Aitken RJ (2016) Oxidative stress and the ethiology of male infertility. J Assist Reprod Genet 33(12):1691–1692
Aitken RJ (2018) Not every sperm is sacred; a perspective on male infertility. Mol Hum Reprod 24(6):287–298
Aitken RJ, Curry BJ (2011) Redox regulation of human sperm function: from the physiological control of sperm capacitation to the etiology of infertility and DNA damage in the germ line. Antioxid Redox Signal 14(3):367–381. https://doi.org/10.1089/ars.2010.3186
Aitken RJ, Paterson M, Fisher H et al (1995) Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function. J Cell Sci 108:2017–2025
Aitken RJ, Gordon E, Harkiss D et al (1998a) Relative impact of oxidative stress on the functional competence and genomic integrity of human spermatozoa. Biol Reprod 59(5):1037–1046
Aitken RJ, Harkiss D, Knox W et al (1998b) A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation. J Cell Sci 111:645–656
Aitken RJ, De Iuliis GN, McLachlan RI (2009) Biological and clinical significance of DNA damage in the male germ line. Int J Androl 32(1):46–56. https://doi.org/10.1111/j.1365-2605.2008.00943.x
Aitken RJ, Jones KT, Robertson SA (2012) Reactive oxygen species and sperm function in sickness and in health. J Androl 33(6):1096–1106. https://doi.org/10.2164/jandrol.112.016535
Aitken RJ, Smith TB, Jobling MS et al (2014) Oxidative stress and male reproductive health. Asian J Androl 16(1):31–38. https://doi.org/10.4103/1008-682X
Aitken RJ, De Iuliis G, Drevet JR (2019) Role of oxidative stress in the etiology of male infertility and the potential therapeutic value of antioxidants. In: Henkel R, Samanta L, Agarwal A (eds) Oxidants, antioxidants, and impact of the oxidative stress in male reproduction. Academic Press-Elsevier, Oxford, UK, pp 90–100
Awda BJ, Buhr MM (2010) Extracellular signal-regulated kinases (ERKs) pathway and reactive oxygen species regulate tyrosine phosphorylation in capacitating boar spermatozoa. Biol Reprod 83(5):750–758. https://doi.org/10.1095/biolreprod.109.082008
Ayala A, Muñoz MF, Argüelles S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Med Cell Longev 2014:1. https://doi.org/10.1155/2014/360438
Bennetts LE, Aitken RJ (2005) A comparative study of oxidative DNA damage in mammalian spermatozoa. Mol Reprod Dev 71(1):77–87
Björndahl L, Kvist U (2010) Human sperm chromatin stabilization: a proposed model including zinc bridges. Mol Hum Reprod 16(1):23–29. https://doi.org/10.1093/molehr/gap099
Brouwers JF, Boerke A, Silva PF et al (2011) Mass spectrometric detection of cholesterol oxidation in bovine sperm. Biol Repord 85(1):128–136. https://doi.org/10.1095/biolreprod.111.091207
Brütsch SH, Wang CC, Li L, Stender H et al (2015) Expression of inactive glutathione peroxidase 4 leads to embryonic lethality, and inactivation of the Alox15 gene does not rescue such knock-in mice. Antioxid Redox Signal 22(4):281–293. https://doi.org/10.1089/ars.2014.5967
Chabory E, Damon C, Lenoir A et al (2009) Epididylis seleno-independent glutathione peroxidase 5 maintains sperm DNA integrity in mice. J Clin Invest 119(7):2074–2085. https://doi.org/10.1172/JCI38940
Champroux A, Damon-Soubeyrand C, Goubely C et al (2018a) Nuclear integrity but not Topology of mouse sperm chromosome is affected by oxidative DNA damage. Genes (Basel);9(10). pii: E501. https://doi.org/10.3390/genes9100501
Champroux A, Cocquet J, Henry-Berger J et al (2018b) A decade of exploring the mammalian sperm Epigenome: paternal epigenetic and transgenerational inheritance. Front Cell Dev Biol 6:50. https://doi.org/10.3389/fcell.2018.00050
Chen Q, Yan M, Cao Z et al (2016) Sperm tsRNAs contribute to intergenerational inheritance of an acquired metabolic disorder. Science 351(6271):397–400. https://doi.org/10.1126/science.aad7977
Cohen-Bacrie P, Belloc S, Ménézo YJ et al (2009) Correlation between DNA damage and sperm parameters: a prospective study of 1,633 patients. Fertil Steril 91(5):1801–1805. https://doi.org/10.1016/j.fertnstert.2008.01.086
Cooper TG, Noonan E, von Eckardstein S et al (2010) World Health Organization reference values for human semen characteristics. Hum Reprod Update 16(3):231–245. https://doi.org/10.1093/humupd/dmp048
De Iuliis GN, Thomson LK, Mitchell LA et al (2009) DNA damage in human spermatozoa is highly correlated with the efficiency of chromatin remodeling and the formation of 8-hydroxy-2′-deoxyguanosine, a marker of oxidative stress. Biol Reprod 81(3):517–524. https://doi.org/10.1095/biolreprod.109.076836
Donà G, Fiore C, Andrisani A et al (2011) Evaluation of correct endogenous reactive oxygen species content for human sperm capacitation and involvement of the NADPH oxidase system. Hum Reprod 26(12):3264–3273. https://doi.org/10.1093/humrep/der321
Drevet JR (2006) The antioxidant glutathione peroxidase family and spermatozoa: a complex story. Mol Cell Endocrinol 250(1–2):70–79
Fernandez MC, O’Flaherty C (2018) Peroxiredoxin 6 is the primary antioxidant enzyme for the maintenance of viability and DNA integrity in human spermatozoa. Hum Reprod 33:1394. https://doi.org/10.1093/humrep/dey221
Gharagozloo P, Aitken RJ (2011) The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. Hum Reprod 26:1628–1640
Gharagozloo P, Gutiérrez-Adán A, Champroux A et al (2016) A novel antioxidant formulation designed to treat male infertility associated with oxidative stress: promising preclinical evidence from animal models. Hum Reprod 31(2):252–262. https://doi.org/10.1093/humrep/dev302
Giwercman A, Lindstedt L, Larsson M et al (2010) Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case-control study. Int J Androl 33(1):e221–e227. https://doi.org/10.1111/j.1365-2605.2009.00995
Henkel RR (2011) Leukocytes and oxidative stress: dilemma for sperm function and male fertility. Asian J Androl 13(1):43–52. https://doi.org/10.1038/aja.2010.76
Houston BJ, Nixon B, King BV et al (2016) The effects of radiofrequency electromagnetic radiation on sperm function. Reproduction 152(6):R263–R276
Houston BJ, Nixon B, Martin JH et al (2018) Heat exposure induces oxidative stress and DNA damage in the male germ line. Biol Reprod 98(4):593–606. https://doi.org/10.1093/biolre/ioy009
Johnson GD, Lalancette C, Linnemann AK et al (2011) The sperm nucleus: chromatin, RNA, and the nuclear matrix. Reproduction 141(1):21–36. https://doi.org/10.1530/REP-10-0322
Jones R, Mann T, Sherins RJ (1978) Adverse effects of peroxidized lipid on human spermatozoa. Proc R Soc Lond B Biol Sci 201(1145):413–417
Jones R, Mann T, Sherins R (1979) Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma. Fertil Steril 31(5):531–537
Kocer A, Henry-Berger J, Noblanc A et al (2015) Oxidative DNA damage in mouse sperm chromosomes: Size matters. Free Radic Biol Med 89:993–1002. https://doi.org/10.1016/j.freeradbiomed
Koppers AJ, Mitchell LA, Wang P et al (2011) Phosphoinositide 3-kinase signalling pathway involvement in a truncated apoptotic cascade associated with motility loss and oxidative DNA damage in human spermatozoa. Biochem J 436(3):687–698. https://doi.org/10.1042/BJ20110114
Leclerc P, de Lamirande E, Gagnon C (1997) Regulation of protein-tyrosine phosphorylation and human sperm capacitation by reactive oxygen derivatives. Free Radic Biol Med 22(4):643–656
Lee KM, Ward MH, Han S et al (2009) Paternal smoking, genetic polymorphisms in CYP1A1 and childhood leukemia risk. Leuk Res 33:250–258
Lenzi A, Picardo M, Gandini L et al (1996) Lipids of the sperm plasma membrane: from polyunsaturated fatty acids considered as markers of sperm function to possible scavenger therapy. Hum Reprod Update 2(3):246–256
Lewis B, Aitken RJ (2001) A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa. J Androl 22(4):611–622
Lewis SE, Boyle PM, McKinney KA et al (1995) Total antioxidant capacity of seminal plasma is different in fertile and infertile men. Fertil Steril 64(4):868–870
Liang R, Senturker S, Shi X et al (1999) Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage. Carcinogenesis 20(5):893–898
McLay DW, Clarke HJ (2003) Remodelling the paternal chromatin at fertilization in mammals. Reproduction 125(5):625–633
Ménézo Y, Dale B, Cohen M (2010) DNA damage and repair in human oocytes and embryos: a review. Zygote 18(4):357–365. https://doi.org/10.1017/S0967199410000286
Moazamian R, Polhemus A, Connaughton H et al (2015) Oxidative stress and human spermatozoa: diagnostic and functional significance of aldehydes generated as a result of lipid peroxidation. Mol Hum Reprod 21(6):502–515. https://doi.org/10.1093/molehr/gav014
Noblanc A, Damon-Soubeyrand C, Karrich B et al (2013) DNA oxidative damage in mammalian spermatozoa: where and why is the male nucleus affected? Free Radic Biol Med 65:719–723. https://doi.org/10.1016/j.freeradbiomed.2013.07.044
O’Flaherty C, de Lamirande E, Gagnon C (2006) Positive role of reactive oxygen species in mammalian sperm capacitation: triggering and modulation of phosphorylation events. Free Radic Biol Med 41(4):528–540
Ohno M, Sakumi K, Fukumura R et al (2014) 8-oxoguanine causes spontaneous de novo germline mutations in mice. Sci Rep 4:4689. https://doi.org/10.1038/srep04689
Sawyer DE, Mercer BG, Wiklendt AM et al (2003) Quantitative analysis of gene-specific DNA damage in human spermatozoa. Mutat Res 529(1–2):21–34
Sharma U, Conine CC, Shea JM et al (2016) Biogenesis and function of tRNA fragments during sperm maturation and fertilization in mammals. Science 351(6271):391–396. https://doi.org/10.1126/science.aad6780
Shoeb M, Ansari NH, Srivastava SK et al (2014) 4-Hydroxynonenal in the pathogenesis and progression of human diseases. Curr Med Chem 21(2):230–237
Smith TB, De Iuliis GN, Lord T et al (2013a) The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line. Reproduction 146(3):253–262. https://doi.org/10.1530/REP-13-0186
Smith TB, Dun MD, Smith ND et al (2013b) The presence of a truncated base excision repair pathway in human spermatozoa that is mediated by OGG1. J Cell Sci 126(Pt 6):1488–1497. https://doi.org/10.1242/jcs.121657
Vorilhon S, Brugnon F, Kocer A et al (2018) Accuracy of human sperm DNA oxidation quantification and threshold determination using an 8-OHdG immuno-detection assay. Hum Reprod 33(4):553–562. https://doi.org/10.1093/humrep/dey038
Wachsman JT (1997) DNA methylation and the association between genetic and epigenetic changes: relation to carcinogenesis. Mutat Res 375(1):1–8
Walters JLH, De Iuliis GN, Dun MD (2018) Pharmacological inhibition of arachidonate 15-lipoxygenase protects human spermatozoa against oxidative stress. Biol Reprod 98(6):784–794. https://doi.org/10.1093/biolre/ioy058
Wu Q, Ni X (2015) ROS-mediated DNA methylation pattern alterations in carcinogenesis. Curr Drug Targets 16(1):13–19
Wu X, Zhang Y (2017) TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 18(9):517–534. https://doi.org/10.1038/nrg.2017.33
Zhao J, Zhang Q, Wang Y et al (2014) Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis. Fertil Steril 102:998–1005
Authors’ Roles
J.R.D. drafted the article, which was then edited and revised by R.J.A. Both authors approved the final version of this article.
Conflict of Interest
J.R.D. and R.J.A. are scientific advisors of a US-based biotech company (Celloxess LLC, New Jersey, USA) which has a commercial interest in the detection and treatment of oxidative stress.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Springer Nature Switzerland AG
About this chapter
Cite this chapter
Drevet, J.R., Aitken, R.J. (2019). Oxidative Damage to Sperm DNA: Attack and Defense. In: Baldi, E., Muratori, M. (eds) Genetic Damage in Human Spermatozoa. Advances in Experimental Medicine and Biology, vol 1166. Springer, Cham. https://doi.org/10.1007/978-3-030-21664-1_7
Download citation
DOI: https://doi.org/10.1007/978-3-030-21664-1_7
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-21663-4
Online ISBN: 978-3-030-21664-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)