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Chapter 22 - Reactive Oxygen Species and Sperm DNA Damage

from Section 4 - Laboratory Evaluation and Treatment of Male Infertility

Published online by Cambridge University Press:  06 December 2023

By
Lesley Haddock ,
Erica Gardiner  and
Sheena E. M. Lewis
Edited by
Douglas T. Carrell ,
Alexander W. Pastuszak  and
James M. Hotaling
Douglas T. Carrell
Affiliation:
Utah Center for Reproductive Medicine
Alexander W. Pastuszak
Affiliation:
University of Utah
James M. Hotaling
Affiliation:
Utah Center for Reproductive Medicine
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Summary

Over the last decade it has become increasingly clear that semen analysis is insufficient to diagnose male infertility. With 30% of infertile men diagnosed as idiopathic, the ethics of continuing to rely on outdated diagnostic parameters must be questioned. Sperm DNA damage is a strong biomarker of male infertility. It also correlates significantly with increased risk of miscarriage after both natural and ART conception. Thirdly, sperm DNA damage is a useful predictive tool for both IVF and ICSI live birth success. DNA fragmentation can occur as double or single strand breaks. Oxidative stress is a common cause of single strand breaks and can be prevented by endogenous and dietary supplemented antioxidants. In contrast, double strand breaks are caused by dysfunction during spermatogenesis, and are harder for oocytes to repair post fertilization. Greater awareness of the relevance of DNA damage and its origins could aid fertility choices and outcomes.

Keywords

men’s healthsperm DNA damagereactive oxygen speciesComet assayTUNEL testingsperm chromatin assaymale aging
Type
Chapter
Information
Men's Reproductive and Sexual Health Throughout the Lifespan
An Integrated Approach to Fertility, Sexual Function, and Vitality
 , pp. 175 - 182
Publisher: Cambridge University Press
Print publication year: 2023

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References

Duca, Y, Calogero, AE, Cannarella, R, Condorelli, RA, La Vignera, S. Current and emerging medical therapeutic agents for idiopathic male infertility. Expert Opin Pharmacother. 2019;20(1):55–67.Google Scholar
Nicopoullos, J, Vicens-Morton, A, Lewis, S, et al. Novel use of COMET parameters of sperm DNA damage may increase its utility to diagnose male infertility and predict live births following both IVF and ICSI. Hum Reprod. 2019;151:1–9.Google Scholar
Dada, R. Sperm DNA damage diagnostics: when and why. Transl Androl Urol. 2017;6(4):S691–S694.Google Scholar
Bui, AD, Sharma, R, Henkel, R, Agarwal, A. Reactive oxygen species impact on sperm DNA and its role in male infertility. Andrologia. 2018;50(8): e13012.CrossRefGoogle ScholarPubMed
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(4):428–432.Google Scholar
Esteves, SC, Santi, D, Simoni, M. An update on clinical and surgical interventions to reduce sperm DNA fragmentation in infertile men. Andrology. 2020;8(1):53–81.Google Scholar
Panner Selvam, MK, Ambar, RF, Agarwal, A, Henkel, R. Etiologies of sperm DNA damage and its impact on male infertility. Andrologia. 2021;53(1): e13706.Google Scholar
Cissen, M, Van Wely, M, Scholten, I, et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta analysis. PLoS ONE. 2016;11(11):e0165125.CrossRefGoogle ScholarPubMed
Brandt, JS, Cruz Ithier, MA, Rosen, T, Ashkinadze, E. Advanced paternal age, infertility, and reproductive risks: a review of the literature. Prenat Diagn. 2019;39(2):81–87.Google Scholar
Horta, F, Vollenhoven, B, Healey, M, Busija, L, Catt, S, Temple-Smith, P. Male ageing is negatively associated with the chance of live birth in IVF/ICSI cycles for idiopathic infertility. Hum Reprod. 2019;34(12):2523–2532.Google Scholar
Ramasamy, R, Chiba, K, Butler, P, Lamb, DJ. Male biological clock: a critical analysis of advanced paternal age. Fertil Steril. 2015;103(6):1402–1406.Google Scholar
van Kooij, RJ, de Boer, P, de Vreeden-Elbertse, JMT, Ganga, NA, Singh, N, te Velde, ER. The neutral comet assay detects double strand DNA damage in selected and unselected human spermatozoa of normospermic donors. Int J Androl. 2004;27(3):140–146.CrossRefGoogle ScholarPubMed
Hoeijmakers, JHJ. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411(6835):366–374.Google Scholar
Agarwal, A, Saleh, RA, Bedaiwy, MA. Role of reactive oxygen species in the pathophysiology of human reproduction. Fertil Steril. 2003;79(4):829–843.Google Scholar
Shamsi, MB, Kumar, R, Dada, R. Evaluation of nuclear DNA damage in human spermatozoa in men opting for assisted reproduction. Indian J Med Res. 2008;127(2):115–123.Google Scholar
Horta, F, Catt, S, Vollenhoven, B, Temple-Smith, P. Oocyte DNA repair capacity of controlled sperm DNA damage is affected by female age. Hum Reprod. 2018;33(2):529–544.Google Scholar
Vyas, L, Lewis, S, Tharakan, T, Jayasena, C, Minhas, S, Ramsay, J. MP75–01 evidence that testicular sperm has improved DNA integrity compared to ejaculated sperm in infertile men. J Urol. 2019;201(4).Google Scholar
Lopes, LS, Esteves, SC. Testicular sperm in non-azoospermic infertile men with oxidatively induced high sperm DNA damage. In: Parekattil, S, Esteves, S, Agarwal, A, eds. Male Infertility. Springer International Publishing; 2020:735–745.CrossRefGoogle Scholar
Lewis, SEM, Kumar, K. The paternal genome and the health of the assisted reproductive technology child. Asian J Androl. 2015;17(4):616–622.Google Scholar
Simon, L, Emery, BR, Carrell, DT. Review: diagnosis and impact of sperm DNA alterations in assisted reproduction. Best Pract Res Clin Obstet Gynaecol. 2017;44:38–56.Google Scholar
McQueen, DB, Zhang, J, Robins, JC. Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2019;112(1):54–60.e3.Google Scholar
Borges, E, Zanetti, BF, Setti, AS, Braga, DP de AF, Provenza, RR, Iaconelli, A. Sperm DNA fragmentation is correlated with poor embryo development, lower implantation rate, and higher miscarriage rate in reproductive cycles of non-male factor infertility. Fertil Steril. 2019;112(3):483–490.Google Scholar
Wdowiak, A, Bakalczuk, S, Bakalczuk, G. The effect of sperm DNA fragmentation on the dynamics of the embryonic development in intracytoplasmatic sperm injection. Reprod Biol. 2015;15(2):94–100.Google Scholar
Wright, C, Milne, S, Leeson, H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod Biomed Online. 2014;28(6):684-703.Google Scholar
Samuel, R, Feng, H, Jafek, A, Despain, D, Jenkins, T, Gale, B. Microfluidic-based sperm sorting & analysis for treatment of male infertility. Transl Androl Urol. 2018;7(3):S336–S347.CrossRefGoogle ScholarPubMed
Kishi, K, Ogata, H, Ogata, S, et al. Frequency of sperm DNA fragmentation according to selection method: comparison and relevance of a microfluidic device and a swim-up procedure. J Clin Diagn Res. 2015;9(11):QC14–QC16.Google Scholar
Yildiz, K, Yuksel, S. Use of microfluidic sperm extraction chips as an alternative method in patients with recurrent in vitro fertilisation failure. J Assist Reprod Genet. 2019;36(7):1423–1429.CrossRefGoogle ScholarPubMed
Esteves, SC, Roque, M. Extended indications for sperm retrieval: summary of current literature. F1000Research. 2019;8.CrossRefGoogle ScholarPubMed
Zhang, J, Xue, H, Qiu, F, Zhong, J, Su, J. Testicular spermatozoon is superior to ejaculated spermatozoon for intracytoplasmic sperm injection to achieve pregnancy in infertile males with high sperm DNA damage. Andrologia. 2019;51(2):e13175.Google Scholar
Drevet, JR, Aitken, RJ. Oxidation of sperm nucleus in mammals: a physiological necessity to some extent with adverse impacts on oocyte and offspring. Antioxidants. 2020;9(2):95.Google Scholar
Martin-Hidalgo, D, Bragado, MJ, Batista, AR, Oliveira, PF, Alves, MG. Antioxidants and male fertility: from molecular studies to clinical evidence. Antioxidants. 2019;8(4):89.Google Scholar
Sanocka, D, Kurpisz, M. Reactive oxygen species and sperm cells. Reprod Biol Endocrinol. 2004;2(1):1–7.Google Scholar
Aktan, G, Doǧru-Abbasoǧlu, S, Küçükgergin, C, Kadioǧlu, A, Özdemirler-Erata, G, Koçak-Toker, N. Mystery of idiopathic male infertility: is oxidative stress an actual risk? Fertil Steril. 2013;99(5):1211–1215.Google Scholar
Khosravi, F, Valojerdi, MR, Amanlou, M, Karimian, L, Abolhassani, F. Relationship of seminal reactive nitrogen and oxygen species and total antioxidant capacity with sperm DNA fragmentation in infertile couples with normal and abnormal sperm parameters. Andrologia. 2014;46(1):17–23.Google Scholar
Shamsi, MB, Kumar, R, Malhotra, N, et al. Chromosomal aberrations, Yq microdeletion, and sperm DNA fragmentation in infertile men opting for assisted reproduction. Mol Reprod Dev. 2012;79(9):637–650.Google Scholar
Aitken, RJ, Jones, KT, Robertson, SA. Reactive oxygen species and sperm function-in sickness and in health. J Androl. 2012;33(6):1096–1106.Google Scholar
O’Flaherty, C. Reactive oxygen species and male fertility. Antioxidants. 2020;9(4):287.Google Scholar
Wright, C, Milne, S, Leeson, H. Sperm DNA damage caused by oxidative stress: modifiable clinical, lifestyle and nutritional factors in male infertility. Reprod Biomed Online. 2014;28(6):684–703.Google Scholar
Lewis, SEM, 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(4):868–870.Google Scholar
Lewis, SEM, Samantha Sterling, EL, Young, IS, Thompson, W. Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men. Fertil Steril. 1997;67(1):142–147.Google Scholar
Mylonas, C, Kouretas, D. Lipid peroxidation and tissue damage. In Vivo (Brooklyn). 1999;13(3):295–309.Google Scholar
Atig, F, Raffa, M, Ben Ali, H, Abdelhamid, K, Saad, A, Ajina, M. Altered antioxidant status and increased lipid per-oxidation in seminal plasma of Tunisian infertile men. Int J Biol Sci. 2011;8(1):139–149.Google Scholar
Sanocka, D, Kurpisz, M. Reactive oxygen species and sperm cells. Reprod Biol Endocrinol. 2004;2:12.Google Scholar
Badouard, C, Ménézo, Y, Panteix, G, et al. Determination of new types of DNA lesions in human sperm. Zygote. 2008;16(1):9–13.Google Scholar
Lamirande, E De, Jiang, H, Zini, A, Kodama, H, Gagnon, C. Reactive oxygen species and sperm physiology. Rev Reprod. 1997;2(1):48–54.Google Scholar
Oehninger, S, Blackmore, P, Mahony, M, Hodgen, G. Effects of hydrogen peroxide on human spermatozoa. J Assist Reprod Genet. 1995;12(1):41–47.Google Scholar
Martins da Silva, SJ. Male infertility and antioxidants: one small step for man, no giant leap for andrology? Reprod Biomed Online. 2019;39(6):879–883.Google Scholar
Smits, RM, Mackenzie-Proctor, R, Yazdani, A, Stankiewicz, MT, Jordan, V, Showell, MG. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;3(3):CD007411.Google Scholar
Agarwal, A, Parekh, N, Selvam, MKP, et al. Male oxidative stress infertility (MOSI): proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J Mens Health. 2019;37(3):296–312.Google Scholar
Ritchie, C, Ko, EY. Oxidative stress in the pathophysiology of male infertility. Andrologia. 2020;53(1):e13581.Google ScholarPubMed

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