Fragmentation of sperm DNA: clinical significance, reasons, methods of evaluation and correction

Abstract

A review of the main causes of male infertility in the aspect of the relationship with the degree of sperm DNA fragmentation is presented. Information is provided on the main methods for assessing sperm DNA fragmentation and its effect on male fertility. The effect of oxidative stress on the integrity of sperm DNA structure, the reparative capabilities of antioxidant therapy, and the effect of varicocele on male fertility are described.

Keywords

sperm DNA fragmentation / assessment methods / oxidative stress / varicocele

References

[1] Лебедев Г.С., Голубев Н.А., Шадеркин И.А. и др. Мужское бесплодие в Российской Федерации: статистические данные за 2000–2018 годы // Экспериментальная и клиническая урология. – 2019. – № 4. – С. 4–13. [Lebedev GS., Golubev NA, Shaderkin IA, et al. Male infertility in the Russian Federation: statistical data for 2000–2018. Experimental and Clinical Urology. 2019;(4):4-13. (In Russ.)]. https://doi.org/10.29188/2222-8543-2019-11-4-4-12.

[2] Inhorn MC, Patrizio P. Infertility around the globe: new thinking on gender, reproductive technologies and global movements in the 21st century. Hum Reprod Update. 2015; 21(4):411-426. https://doi.org/10.1093/humupd/dmv016.

[3] Руднева С.А., Брагина Е.Е., Арифулин Е.А. и др. Фрагментация ДНК в сперматозоидах и ее взаимосвязь с нарушением сперматогенеза // Андрология и генитальная хирургия. – 2014. – Т. 15. – № 4. – С. 26–33. [Rudneva SA., Bragina EE, Arifulin EA, et al. DNA fragmentation in spermatozoa and its relationship with impaired spermatogenesis. Andrology and Genital Surgery. 2014;15(4):26-33. (In Russ.)]. https://doi.org/10.17650/2070-9781-2014-4.

[4] Agarwal A, Mulgund A, Hamada A, et al. A unique view on male infertility around the globe. Reprod Biol Endocrinol. 2015;13:37. https://doi.org/10.1186/s12958-015-0032-1.

[5] Jungwirth A, Giwercman A, Tournaye H, et al. European Association of Urology guidelines on Male Infertility: the 2012 update. Eur Urol. 2012;62(2):324-332. https://doi.org/10.1016/j.eururo.2012.04.048.

[6] Аль-Шукри С.Х., Боровец С.Ю., Торопов В.А. Нарушение сперматогенеза и исходы вспомогательных репродуктивных технологий при различных формах гипогонадизма // Урологические ведомости. – 2016. – Т. 6. – № 1. – С. 21–28. [Al-Shukri SH, Borovets SYu, Toropov VA. Violation of spermatogenesis and outcomes of assisted reproductive technologies in various forms of hypogonadism. Urologicheskie vedomosti. 2016;6(1):21-28. (In Russ)]. https://doi.org/10.17816/uroved621-28.

[7] Hanson BM, Eisenberg ML, Hotaling JM. Male infertility: a biomarker of individual and familial cancer risk. Fertil Steril. 2018;109(1): 6-19. https://doi.org/10.1016/j.fertnstert.2017.11.005.

[8] Krausz C, Riera-Escamilla A. Genetics of male infertility. Nat Rev Urol. 2018;15(6):369-384. https://doi.org/10.1038/s41585-018-0003-3.

[9] Menezo YJ, Silvestris E, Dale B, et al. Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction. Reprod Biomed Online. 2016;33(6):668-683. https://doi.org/10.1016/j.rbmo.2016.09.006.

[10] Cissen M, Wely MV, 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. https://doi.org/10.1371/journal.pone.0165125.

[11] Tarín JJ, García-Pérez MA, Cano A. Assisted reproductive technology results: why are livebirth percentages so low? Mol. Reprod. Dev. 2014;81(7):568-583. https://doi.org/10.1002/mrd.22340.

[12] Cassuto NG, Hazout A, Bouret D, et al. Low birth defects by deselecting abnormal spermatozoa before ICSI. Reprod. Biomed. Online. 2014;28(1):47-53. https://doi.org/10.1016/j.rbmo.2013.08.013.

[13] Bach PV, Schlegel PN. Sperm DNA damage and its role in IVF and ICSI. Basic Clin Androl. 2016;26:15. https://doi.org/10.1186/s12610-016-0043-6.

[14] Khadem N, Poorhoseyni A, Jalali M, et al. Sperm DNA fragmentation in couples with unexplained recurrent spontaneous abortions. Andrologia. 2014;46(2):126-130. https://doi.org/10.1111/and.12056.

[15] Verhaeghe F, Di Pizio P, Bichara C, et al. Cannabis consumption might exert deleterious effects on sperm nuclear quality in infertile men. Reprod Biomed Online. 2020;40(2):270-280. https://doi.org/10.1016/j.rbmo.2019.11.002.

[16] Gunes S, Al-Sadaan M, Agarwal A. Spermatogenesis, DNA damage and DNA repair mechanisms in male infertility. Reprod Biomed Online. 2015;31(3):309-319. https://doi.org/10.1016/j.rbmo.2015.06.010.

[17] Коршунов М.Н., Коршунова Е.С. Селективные ингибиторы обратного захвата серотонина и фертильный потенциал мужчины. Психиатрия и урология. На стыке смежных дисциплин // Урологические ведомости. – 2016. – Т. 6. – № 3. – С. 19–25. [Korshunov MN, Korshunova ES. Selective serotonin reuptake inhibitor and fertility potential of the men. Psychiatry and Urology. At the junction of related disciplines. Urologicheskie vedomosti. 2016;6(3):19-25. (In Russ.)]. https://doi.org/10.17816/uroved6319-25.

[18] Agarwal A, Rana M, Qiu E, et al. Role of oxidative stress, infection and inflammation in male infertility. Andrologia. 2018;50(11): e13126. https://doi.org/10.1111/and.13126.

[19] Ribeiro S, Sharma R, Gupta S, et al. Inter- and intra-laboratory standardization of TUNEL assay for assessment of sperm DNA fragmentation. Andrology. 2017;5(3):477-485. https://doi.org/10.1111/andr.12334.

[20] Zini A, Albert O, Robaire B. Assessing sperm chromatin and DNA damage: clinical importance and development of standards. Andrology. 2014;2(3):322-325. https://doi.org/10.1111/j.2047-2927.2014.00193.x.

[21] Majzoub А, Esteves S, Gosálvez J, et al. Specialized sperm function tests in varicocele and the future of andrology laboratory. Asian J Androl. 2016;18(2):205-212. https://doi.org/10.4103/1008-682X.172642.

[22] 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. https://doi.org/10.1111/andr.12724.

[23] Arifulin EA, Bragina EE, Kurilo LF, et al. High-throughput analysis of TUNEL-stained sperm using image cytometry. Cytometry. 2017;91(9):854-858. https://doi.org/10.1002/cyto.a.23164.

[24] Das L, Parbin S, Pradhan N, et al. Epigenetics of reproductive infertility. Front Biosci (Schol Ed). 2017;9:509-535. https://doi.org/10.2741/s497.

[25] Gupta S, Sharma R, Agarwal A. Inter-and intra-laboratory standardization of TUNEL assay for assessment of sperm DNA Fragmentation. Curr Protoc Toxicol. 2017;74:16.11.1-16.11.22. https://doi.org/10.1002/cptx.37.

[26] Evenson DP. The Sperm Chromatin Structure Assay (SCSA®) and other sperm DNA fragmentation tests for evaluation of sperm nuclear DNA integrity as related to fertility. Anim Reprod Sci. 2016;169: 56-75. https://doi.org/10.1016/j.anireprosci.2016.01.017.

[27] Simon L, Murphy K, Shamsi MB, et al. Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod. 2014;29(11):2402-2412. https://doi.org/10.1093/humrep/deu228.

[28] Moskovtsev SI, Willis J, Mullen JB. Age-related decline in sperm deoxyribonucleic acid integrity in patients evaluated for male infertility. Fertil Steril. 2006;85(2):496-499. https://doi.org/10.1016/j.fertnstert.2005.05.075.

[29] Johnson SL, Dunleavya J, Gemmell NJ, Nakagawa S. Consistent age-dependent declines in human semen quality: A systematic review and meta-analysis. Ageing Res Rev. 2015;19:22-33. https://doi.org/ 10.1016/j.arr.2014.10.007.

[30] Овчинников Р.И., Попова А.Ю., Гамидов С.И., Квасов А.В. Антиоксидантная терапия — ключ к лечению идиопатического мужского бесплодия // Медицинский Совет. – 2017. – № 20. – 177–181. [Ovchinnikov RI, Popova AYu, Gamidov SI, Kvasov AV. Antioxidant therapy is the key to the treatment of idiopathic male infertility. Medical Council. 2017;(20):177-181. (In Russ.)]. https://doi.org/10.21518/2079-701X-2017-20-177-181.

[31] Jannatifar R, Parivar K, Roodbari NH, et al. Effects of N-acetyl-cysteine supplementation on sperm quality, chromatin integrity and level of oxidative stress in infertile men. Reprod Biol Endocrinol. 2019;17:24. https://doi.org/10.1186/s12958-019-0468-9.

[32] Pourmand G, Movahedin M, Dehghani S, et al. Does L-carnitine therapy add any extra benefit to standard inguinal varicocelectomy in terms of deoxyribonucleic acid damage or sperm quality factor indices: a randomized study. Urology. 2014;84(4):821-825. https://doi.org/10.1016/j.urology.2014.07.006.

[33] Калинина С.Н., Кореньков Д.Г., Фесенко В.Н. Лечение сперматологических нарушений и оксидативного стресса после перенесенных репродуктивно значимых заболеваний, вызванных инфекциями, передающимися половым путем // Урологические ведомости. – 2018. – Т. 8. – № 4. – C. 5–15. [Kalinina SN, Korenkov DG, Fesenko VN. Treatment of spermatologic disorders and oxidative stress after reproductively significant diseases caused by sexually transmitted infection. Urologicheskie vedomosti. 2018;8(4):5-15. (In Russ.)]. https://doi.org/10.17816/uroved845-15.

[34] Barazani Y, Agrawal A, Sabanegh ES. Jr. Functional sperm testing and the role of proteomics in the evaluation of male infertility. Urology. 2014;84(2):255-61. https://doi.org/10.1016/j.urology.2014.04.043.

[35] Elbardisi H, Finelli R, Agarwal A, et al. Predictive value of oxidative stress testing in semen for sperm DNA fragmentation assessed by sperm chromatin dispersion test. Andrology. 2019;11. https://doi.org/10.1111/andr.12743.

[36] Попова А.Ю., Гамидов С.И., Овчинников Р.И. и др. Опыт применения докозагексаеновой кислоты (Бруди Плюс) у пациентов с повышенным индексом фрагментации ДНК сперматозоидов в научном центре акушерства, гинекологии и перинатологии им. акад. В.И. Кулакова // Андрология и генитальная хирургия. – 2015. – Т. 16. – № 2. – С. 51–55 [Popova AYu, Gamidov SI, Ovchinnikov RI, et al. Experience in the use of docosahexaenoic acid (BrudiPlus) in patients with increased sperm DNA fragmentation index in Acad. V.I. Kulakov Research Center for Obstetrics, Gynecology and Perinatology. Andrology and Genital Surgery. 2015;16(2):51-55. (In Russ.)]. https://doi.org/10.17650/2070-9781-2015-2.

[37] Majzoub A, Agarwal A. Systematic review of antioxidant types and doses in male infertility: Benefits on semen parameters, advanced sperm function, assisted reproduction and live-birth rate. Arab J Urol. 2018;16(1):113-124. https://doi.org/10.1016/j.aju.2017.11.013.

[38] Henkel R, Sandhu S, Agarwal A. The excessive use of antioxidant therapy: A possible cause of male infertility? Andrologia. 2019;51(1): e13162. https://doi.org/10.1111/and.13162.

[39] Smits RM, Mackenzie-Proctor R, Yazdani A, et al. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2019;14(3): CD007411. https://doi.org/10.1002/14651858.CD007411.pub4.

[40] Showell MG, Brown J, Yazdani A, et al. Antioxidants for male subfertility. Cochrane Database Syst Rev. 2014;12: CD007411. https://doi.org/10.1002/14651858.CD007411.

[41] Овчинников Р.И., Гамидов С.И., Попова А.Ю. и др. Причины репродуктивных потерь у мужчин — фрагментация ДНК сперматозоидов // Русский медицинский журнал. – 2015. – № 4. – С. 634. [Ovchinnikov RI, Gamidov SI, Popova AYu, et al. Prichiny reproduktivnykh poter’ u muzhchin – fragmentatsiya DNK spermatozoidov. Russian Medical Journal. 2015;(4):634. (In Russ.)].

RIGHTS & PERMISSIONS

Borovets S.Y., Egorova V.A., Gzgzian A.M., Al-Shukri S.K.