Mechanisms and Clinical Relevance of Sperm DNA Damage

doi:10.12280/gjszjk.20220473

Abstract

Abstract:

Spermatogenesis is an important process for maintaining and promoting male fertility, involving a variety of cell types, regulatory molecules, repair mechanisms and epigenetic regulators. In the later stage of spermatogenesis, the dysfunction of the sperm DNA repair system and the excessive production of reactive oxygen species may damage the nucleus and mitochondrial DNA, causing abnormal spermatogenesis and apoptosis and reducing the probability of natural conception. The sources of sperm DNA damage mainly include replication errors and sperm DNA fragmentation (SDF), which may be related to male infertility, assisted reproduction outcomes, and the growth and development of offspring. The sperm DNA damage can be evaluated by measuring SDF level. Studying the occurrence and mechanisms of sperm DNA damage can help to improve the clinical outcomes in infertile patients. This article reviews the processes of spermatogenesis, spermatogonia regulation and sperm differentiation, and introduces the DNA damage and its impact on the assisted reproduction outcomes.

Key words: DNA damage, Oxidative stress, Spermatogenesis, Reproductive techniques, assisted, Infertility, male

CHEN Ruo-lin, ZHANG Yun-shan. Mechanisms and Clinical Relevance of Sperm DNA Damage[J]. Journal of International Reproductive Health/Family Planning, 2023, 42(2): 130-134.

References 35

[1]	Kuchakulla M, Narasimman M, Khodamoradi K, et al. How defective spermatogenesis affects sperm DNA integrity[J]. Andrologia, 2021, 53(1):e13615. doi: 10.1111/and.13615. doi: 10.1111/and.13615
[2]	Simon L, Murphy K, Shamsi MB, et al. Paternal influence of sperm DNA integrity on early embryonic development[J]. Hum Reprod, 2014, 29(11):2402-2412. doi: 10.1093/humrep/deu228. doi: 10.1093/humrep/deu228 URL
[3]	Tímermans A, Vázquez R, Otero F, et al. DNA fragmentation of human spermatozoa: Simple assessment of single- and double-strand DNA breaks and their respective dynamic behavioral response[J]. Andrology, 2020, 8(5):1287-1303. doi: 10.1111/andr.12819. doi: 10.1111/andr.12819 pmid: 32416007
[4]	Zhang Y, Zhang W, Wu X, et al. Effect of varicocele on sperm DNA damage: A systematic review and meta-analysis[J]. Andrologia, 2022, 54(1):e14275. doi: 10.1111/and.14275. doi: 10.1111/and.14275
[5]	Ribas-Maynou J, Benet J. Single and Double Strand Sperm DNA Damage: Different Reproductive Effects on Male Fertility[J]. Genes(Basel), 2019, 10(2):105. doi: 10.3390/genes10020105. doi: 10.3390/genes10020105
[6]	Bibi R, Jahan S, Razak S, et al. Protamines and DNA integrity as a biomarkers of sperm quality and assisted conception outcome[J]. Andrologia, 2022, 54(6):e14418. doi: 10.1111/and.14418. doi: 10.1111/and.14418
[7]	Zhu W, Jiang L, Pan C, et al. Deoxyribonucleic acid methylation signatures in sperm deoxyribonucleic acid fragmentation[J]. Fertil Steril, 2021, 116(5):1297-1307. doi: 10.1016/j.fertnstert.2021.06.025. doi: 10.1016/j.fertnstert.2021.06.025 pmid: 34253331
[8]	Hekim N, Gunes S, Asci R, et al. Semiquantitative promoter methylation of MLH1 and MSH2 genes and their impact on sperm DNA fragmentation and chromatin condensation in infertile men[J]. Andrologia, 2021, 53(1):e13827. doi: 10.1111/and.13827. doi: 10.1111/and.13827
[9]	Gunes S, Al-Sadaan M, Agarwal A. Spermatogenesis, DNA damage and DNA repair mechanisms in male infertility[J]. Reprod Biomed Online, 2015, 31(3):309-319. doi: 10.1016/j.rbmo.2015.06.010. doi: 10.1016/j.rbmo.2015.06.010 pmid: 26206278
[10]	Huang C, Gong H, Mu B, et al. BAF-L Modulates Histone-to-Protamine Transition during Spermiogenesis[J]. Int J Mol Sci, 2022, 23(4): 1985. doi: 10.3390/ijms23041985. doi: 10.3390/ijms23041985 URL
[11]	Gustafson EA, Seymour KA, Sigrist K, et al. ZFP628 Is a TAF4b-Interacting Transcription Factor Required for Mouse Spermiogenesis[J]. Mol Cell Biol, 2020, 40(7):e00228-19. doi: 10.1128/MCB.00228-19. doi: 10.1128/MCB.00228-19
[12]	Fraczek M, Lewandowska A, Budzinska M, et al. The Role of Seminal Oxidative Stress Scavenging System in the Pathogenesis of Sperm DNA Damage in Men Exposed and Not Exposed to Genital Heat Stress[J]. Int J Environ Res Public Health, 2022, 19(5):2713. doi: 10.3390/ijerph19052713. doi: 10.3390/ijerph19052713 URL
[13]	Sharma R, Harlev A, Agarwal A, et al. Cigarette Smoking and Semen Quality: A New Meta-analysis Examining the Effect of the 2010 World Health Organization Laboratory Methods for the Examination of Human Semen[J]. Eur Urol, 2016, 70(4):635-645. doi: 10.1016/j.eururo.2016.04.010. doi: S0302-2838(16)30069-0 pmid: 27113031
[14]	Berg E, Houska P, Nesheim N, et al. Chronic Prostatitis/Chronic Pelvic Pain Syndrome Leads to Impaired Semen Parameters, Increased Sperm DNA Fragmentation and Unfavorable Changes of Sperm Protamine mRNA Ratio[J]. Int J Mol Sci, 2021, 22(15):7854. doi: 10.3390/ijms22157854. doi: 10.3390/ijms22157854 URL
[15]	Hologlu D, Gunes S, Asci R, et al. Association among sperm chromatin condensation, sperm DNA fragmentation and 8-OHdG in seminal plasma and semen parameters in infertile men with oligoasthenoteratozoospermia[J]. Andrologia, 2022, 54(1):e14268. doi: 10.1111/and.14268. doi: 10.1111/and.14268
[16]	Liu KS, Mao XD, Pan F, et al. Application of leukocyte subsets and sperm DNA fragment rate in infertile men with asymptomatic infection of genital tract[J]. Ann Palliat Med, 2021, 10(2):1021. doi: 10.21037/apm-19-597. doi: 10.21037/apm-19-597 URL
[17]	Monteiro BS, Freire-Brito L, Carrageta DF, et al. Mitochondrial Uncoupling Proteins (UCPs) as Key Modulators of ROS Homeostasis: A Crosstalk between Diabesity and Male Infertility?[J]. Antioxidants(Basel), 2021, 10(11):1746. doi: 10.3390/antiox 10111746. doi: 10.3390/antiox 10111746
[18]	Ferigolo PC, Ribeiro de Andrade MB, Camargo M, et al. Sperm functional aspects and enriched proteomic pathways of seminal plasma of adult men with obesity[J]. Andrology, 2019, 7(3):341-349. doi: 10.1111/andr.12606. doi: 10.1111/andr.12606 pmid: 30891897
[19]	Shafiei-Roudbari SK, Malekinejad H, Janbaz-Aciabar H, et al. Crosstalk between E2F1 and P53 transcription factors in doxorubicin-induced DNA damage: evidence for preventive/protective effects of silymarin[J]. J Pharm Pharmacol, 2017, 69(9):1116-1124. doi: 10.1111/jphp.12745. doi: 10.1111/jphp.12745 URL
[20]	Sharma V, Collins LB, Chen TH, et al. Oxidative stress at low levels can induce clustered DNA lesions leading to NHEJ mediated mutations[J]. Oncotarget, 2016, 7(18):25377-25390. doi: 10.18632/oncotarget.8298. doi: 10.18632/oncotarget.8298 pmid: 27015367
[21]	Rahbar S, Novin MG, Alizadeh E, et al. New insights into the expression profile of MicroRNA-34c and P53 in infertile men spermatozoa and testicular tissue[J]. Cell Mol Biol(Noisy-le-grand), 2017, 63(8):77-83. doi: 10.14715/cmb/2017.63.8.17. doi: 10.14715/cmb/2017.63.8.17
[22]	Guo H, Chen L, Cui H, et al. Research Advances on Pathways of Nickel-Induced Apoptosis[J]. Int J Mol Sci, 2015, 17(1):10. doi: 10.3390/ijms17010010. doi: 10.3390/ijms17010010 URL
[23]	Practice Committee of the American Society for Reproductive Medicine. Diagnostic evaluation of the infertile male: a committee opinion[J]. Fertil Steril, 2015, 103(3):e18-e25. doi: 10.1016/j.fertnstert.2014.12.103. doi: 10.1016/j.fertnstert.2014.12.103
[24]	Ambar RF, Agarwal A, Majzoub A, et al. The Use of Testicular Sperm for Intracytoplasmic Sperm Injection in Patients with High Sperm DNA Damage: A Systematic Review[J]. World J Mens Health, 2021, 39(3):391-398. doi: 10.5534/wjmh.200084. doi: 10.5534/wjmh.200084 URL
[25]	Cortés-Gutiérrez EI, Fernández JL, Dávila-Rodríguez MI, et al. Two-Tailed Comet Assay (2T-Comet): Simultaneous Detection of DNA Single and Double Strand Breaks[J]. Methods Mol Biol, 2017, 1560:285-293. doi: 10.1007/978-1-4939-6788-9_22. doi: 10.1007/978-1-4939-6788-9_22 pmid: 28155163
[26]	Simon L, Emery B, Carrell DT. Sperm DNA Fragmentation: Consequences for Reproduction[J]. Adv Exp Med Biol, 2019, 1166:87-105. doi: 10.1007/978-3-030-21664-1_6. doi: 10.1007/978-3-030-21664-1_6 pmid: 31301048
[27]	Sugihara A, Van Avermaete F, Roelant E, et al. The role of sperm DNA fragmentation testing in predicting intra-uterine insemination outcome: A systematic review and meta-analysis[J]. Eur J Obstet Gynecol Reprod Biol, 2020, 244:8-15. doi: 10.1016/j.ejogrb.2019.10.005. doi: S0301-2115(19)30447-6 pmid: 31707171
[28]	Steiner AZ, Hansen KR, Barnhart KT, et al. The effect of antioxidants on male factor infertility: the Males, Antioxidants, and Infertility (MOXI) randomized clinical trial[J]. Fertil Steril, 2020, 113(3):552-560.e3. doi: 10.1016/j.fertnstert.2019.11.008. doi: S0015-0282(19)32547-6 pmid: 32111479
[29]	Simon L, Zini A, Dyachenko A, et al. A systematic review and meta-analysis to determine the effect of sperm DNA damage on in vitro fertilization and intracytoplasmic sperm injection outcome[J]. Asian J Androl, 2017, 19(1):80-90. doi: 10.4103/1008-682X.182822. doi: 10.4103/1008-682X.182822 pmid: 27345006
[30]	Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing: a guideline[J]. Fertil Steril, 2013, 99(3):673-677. doi: 10.1016/j.fertnstert.2012.12.049. doi: 10.1016/j.fertnstert.2012.12.049 pmid: 23391408
[31]	Zhao J, Zhang Q, Wang Y, et al. 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[J]. Fertil Steril, 2014, 102(4):998-1005. e8. doi: 10.1016/j.fertnstert.2014.06.033. doi: 10.1016/j.fertnstert.2014.06.033 URL
[32]	Ribas-Maynou J, Yeste M, Becerra-Tomás N, et al. Clinical implications of sperm DNA damage in IVF and ICSI: updated systematic review and meta-analysis[J]. Biol Rev Camb Philos Soc, 2021, 96(4):1284-1300. doi: 10.1111/brv.12700. doi: 10.1111/brv.12700 pmid: 33644978
[33]	Liperis G, Sharma K, Ammar OF, et al. #ESHREjc report: are sperm selection techniques a panacea? Indications for the use of physiological intracytoplasmic sperm injection (PICSI) in medically assisted reproduction[J]. Hum Reprod, 2022, 37(10):2492-2496. doi: 10.1093/humrep/deac182. doi: 10.1093/humrep/deac182 URL
[34]	Ganeva R, Parvanov D, Velikova D, et al. Sperm morphology and DNA fragmentation after zona pellucida selection[J]. Reprod Fertil, 2021, 2(3):221-230. doi: 10.1530/RAF-21-0041. doi: 10.1530/RAF-21-0041 pmid: 35118392
[35]	Panner Selvam MK, Ambar RF, Agarwal A, et al. Etiologies of sperm DNA damage and its impact on male infertility[J]. Andrologia, 2021, 53(1):e13706. doi: 10.1111/and.13706. doi: 10.1111/and.13706