The Negative Impact of Varicocele on Basic Semen Parameters, Sperm Nuclear DNA Dispersion and Oxidation-Reduction Potential in Semen

Kamil Gill, Michal Kups, Patryk Harasny, Tomasz Machalowski, Marta Grabowska, Mariusz Lukaszuk, Marcin Matuszewski, Ewa Duchnik, Monika Fraczek, Maciej Kurpisz, Malgorzata Piasecka, Kamil Gill, Michal Kups, Patryk Harasny, Tomasz Machalowski, Marta Grabowska, Mariusz Lukaszuk, Marcin Matuszewski, Ewa Duchnik, Monika Fraczek, Maciej Kurpisz, Malgorzata Piasecka

Abstract

Since varicocele is so common in infertile men, this study intends to analyse the relationships between varicocele and conventional semen characteristics, sperm nuclear DNA dispersion and oxidation-reduction potential (ORP) in semen. Varicocele-positive and varicocele-negative infertile men (study groups) showed significantly lower standard sperm parameters and higher sperm DNA fragmentation (SDF) and ORP in semen than healthy volunteers and subjects with proven fertility (control groups). A lower proportion of low SDF levels (0-15% SDF) and higher incidence of high SDF levels (>30% SDF), as well as a higher prevalence of high ORP values (>1.37 mV/106 sperm/mL), were found in the study groups vs. the control groups. Moreover, infertile men had significantly lower odds ratios (ORs) for low SDF levels and significantly higher ORs for high SDF levels and high ORP. SDF and ORP were negatively correlated with sperm number, morphology, motility and vitality. Furthermore, a significant positive correlation was found between SDF and ORP. The obtained results suggest that disorders of spermatogenesis may occur in varicocele-related infertility. These abnormalities are manifested not only by reduced standard semen parameters but also by decreased sperm DNA integrity and simultaneously increased oxidative stress in semen.

Keywords: infertility; oxidative stress; sperm DNA fragmentation; varicocele.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Study design, results and suggested pathomechanism associated with abnormalities of spermatogenesis in varicocele subjects.
Figure 2
Figure 2
Micrograph of sperm chromatin dispersion test (SCD) results obtained by light microscopy. Sperm cells with large halos (green arrow) and medium-sized halos (yellow arrow) have normal integrity of nuclear DNA, and sperm cells with small halos (orange arrow), without halos (red arrow) or without halos and degraded chromatin (violet arrow) have fragmented nuclear DNA.

References

    1. Agarwal A., Parekh N., Selvam M.K.P., Henkel R., Shah R., Homa S.T., Ramasamy R., Ko E., Tremellen K., Esteves S., et al. Male oxidative stress infertility (MOSI): Proposed terminology and clinical practice guidelines for management of idiopathic male infertility. World J. Men’s Heal. 2019;37:296–312. doi: 10.5534/wjmh.190055.
    1. Agarwal A., Barbăroșie C., Ambar R., Finelli R. The impact of single-and double-strand dna breaks in human spermatozoa on assisted reproduction. Int. J. Mol. Sci. 2020;21:3882. doi: 10.3390/ijms21113882.
    1. Agarwal A., Baskaran S., Parekh N., Cho C.L., Henkel R., Vij S., Arafa M., Panner Selvam M.K., Shah R. Male infertility. Lancet. 2021;397:319–333. doi: 10.1016/S0140-6736(20)32667-2.
    1. Freeman S., Bertolotto M., Richenberg J., Belfield J., Dogra V., Huang D.Y., Lotti F., Markiet K., Nikolic O., Ramanathan S., et al. Ultrasound evaluation of varicoceles: Guidelines and recommendations of the European Society of Urogenital Radiology Scrotal and Penile Imaging Working Group (ESUR-SPIWG) for detection, classification, and grading. Eur. Radiol. 2020;30:11–25. doi: 10.1007/s00330-019-06280-y.
    1. Lewis S.E.M., Esteves S.C. What does a varicocele do to a man’s fertility? There is much more than meets the eye. Int. Braz. J. Urol. 2021;47:284–286. doi: 10.1590/s1677-5538.ibju.2019.0827.1.
    1. Salonia A., Bettocchi C., Carvalho J., Corona G., Jones T.H., Kadioglu A., Martinez-Salamanca J.I., Minhas S., Serefoglu E.C., Verze P., et al. Sexual and Reproductive Health EAU Guidelines. European Association of Urology; Arnhem, The Netherlands: 2021.
    1. Panner Selvam M.K., Agarwal A. Sperm and seminal plasma proteomics: Molecular changes associated with varicocele-mediated male infertility. World J. Mens Health. 2020;37:472–483. doi: 10.5534/wjmh.190018.
    1. Su J.S., Farber N.J., Vij S.C. Pathophysiology and treatment options of varicocele: An overview. Andrologia. 2021;53 doi: 10.1111/and.13576.
    1. Ren W., Qu J., Xue B., Hu J., Zu X. Infertility duration and pre-operative sperm progressive motility are significant factors of spontaneous pregnancy after varicocele repair. Am. J. Reprod. Immunol. 2020;84:1–7. doi: 10.1111/aji.13318.
    1. Qiu D., Shi Q., Pan L. Efficacy of varicocelectomy for sperm DNA integrity improvement: A meta-analysis. Andrologia. 2021;53 doi: 10.1111/and.13885.
    1. Asafu-Adjei D., Judge C., Deibert C.M., Li G., Stember D., Stahl P.J. Systematic Review of the Impact of Varicocele Grade on Response to Surgical Management. J. Urol. 2020;203:48–56. doi: 10.1097/JU.0000000000000311.
    1. Birowo P., Wijaya J.R., Atmoko W., Rasyid N. The effects of varicocelectomy on the DNA fragmentation index and other sperm parameters: A meta-analysis. Basic Clin. Androl. 2020;30:1–9. doi: 10.1186/s12610-020-00112-6.
    1. Camargo M., Ibrahim E., Intasqui P., Belardin L.B., Antoniassi M.P., Lynne C.M., Brackett N.L., Bertolla R.P. Seminal inflammasome activity in the adult varicocele. Hum. Fertil. 2021:1–15. doi: 10.1080/14647273.2020.1870756.
    1. Dave P., Farber N., Vij S. Conventional semen analysis and advanced sperm function tests in diagnosis and management of varicocele. Andrologia. 2021;53 doi: 10.1111/and.13629.
    1. Fathi A., Mohamed O., Mahmoud O., Alsagheer G.A., Reyad A.M., Abolyosr A., Abdel-Kader M.S., Saber-Khalaf M. The impact of varicocelectomy on sperm DNA fragmentation and pregnancy rate in subfertile men with normal semen parameters: A pilot study. Arab J. Urol. 2021;19:186–190. doi: 10.1080/2090598X.2021.1889746.
    1. Lara-Cerrillo S., Gual-Frau J., Benet J., Abad C., Prats J., Amengual M.J., García-Peiró A. Microsurgical varicocelectomy effect on sperm telomere length, DNA fragmentation and seminal parameters. Hum. Fertil. 2020:1–7. doi: 10.1080/14647273.2019.1711204.
    1. Maheshwari A., Muneer A., Lucky M., Mathur R., McEleny K. A review of varicocele treatment and fertility outcomes. Hum. Fertil. 2020:1–8. doi: 10.1080/14647273.2020.1785117.
    1. Afshar K., Domes T. Varicocele. Can. Urol. Assoc. J. 2018;12:34–36. doi: 10.5489/cuaj.5231.
    1. Moazzam A., Sharma R., Agarwal A. Relationship of spermatozoal DNA fragmentation with semen quality in varicocele-positive men. Andrologia. 2015;47:935–944. doi: 10.1111/and.12360.
    1. Ata-abadi N.S., Mowla S.J., Aboutalebi F., Dormiani K., Kiani-Esfahani A., Tavalaee M., Nasr-Esfahani M.H. Hypoxia-related long noncoding RNAs are associated with varicocele-related male infertility. PLoS ONE. 2020;15:1–12. doi: 10.1371/journal.pone.0232357.
    1. Esteves S.C., Santi D., Simoni M. An update on clinical and surgical interventions to reduce sperm DNA fragmentation in infertile men. Andrology. 2020;8:53–81. doi: 10.1111/andr.12724.
    1. Esteves S.C., Zini A., Coward R.M., Evenson D.P., Gosálvez J., Lewis S.E.M., Sharma R., Humaidan P. Sperm DNA fragmentation testing: Summary evidence and clinical practice recommendations. Andrologia. 2021;53:1–41. doi: 10.1111/and.13874.
    1. Panner Selvam M.K., Ambar R.F., Agarwal A., Henkel R. Etiologies of sperm DNA damage and its impact on male infertility. Andrologia. 2021;53:1–15. doi: 10.1111/and.13706.
    1. Ammar O., Tekeya O., Hannachi I., Sallem A., Haouas Z., Mehdi M. Increased Sperm DNA Fragmentation in Infertile Men with Varicocele: Relationship with Apoptosis, Seminal Oxidative Stress, and Spermatic Parameters. Reprod. Sci. 2021;28:909–919. doi: 10.1007/s43032-020-00311-6.
    1. Baskaran S., Finelli R., Agarwal A., Henkel R. Reactive oxygen species in male reproduction: A boon or a bane? Andrologia. 2021;53 doi: 10.1111/and.13577.
    1. Jeremias J.T., Belardin L.B., Okada F.K., Antoniassi M.P., Fraietta R., Bertolla R.P., Intasqui P. Oxidative origin of sperm DNA fragmentation in the adult varicocele. Int. Braz. J. Urol. 2021;47:275–283. doi: 10.1590/s1677-5538.ibju.2019.0827.
    1. Ribas-Maynou J., Yeste M., Becerra-Tomás N., Aston K.I., James E.R., Salas-Huetos A. Clinical implications of sperm DNA damage in IVF and ICSI: Updated systematic review and meta-analysis. Biol. Rev. 2021 doi: 10.1111/brv.12700.
    1. Tanaka T., Kobori Y., Terai K., Inoue Y., Osaka A., Yoshikawa N., Shimomura Y., Suzuki K., Minami T., Iwahata T., et al. Seminal oxidation–reduction potential and sperm DNA fragmentation index increase among infertile men with varicocele. Hum. Fertil. 2020:1–5. doi: 10.1080/14647273.2020.1712747.
    1. Abdelbaki S.A., Sabry J.H., Al-Adl A.M., Sabry H.H. The impact of coexisting sperm DNA fragmentation and seminal oxidative stress on the outcome of varicocelectomy in infertile patients: A prospective controlled study. Arab J. Urol. 2017;15:131–139. doi: 10.1016/j.aju.2017.03.002.
    1. Al Omrani B., Al Eisa N., Javed M., Al Ghedan M., Al Matrafi H., Al Sufyan H. Associations of sperm DNA fragmentation with lifestyle factors and semen parameters of Saudi men and its impact on ICSI outcome. Reprod. Biol. Endocrinol. 2018;16:1–6. doi: 10.1186/s12958-018-0369-3.
    1. Evenson D.P. Evaluation of sperm chromatin structure and DNA strand breaks is an important part of clinical male fertility assessment. Transl. Androl. Urol. 2017;6:S495–S500. doi: 10.21037/tau.2017.07.20.
    1. Cheng H., Han M., Ding J., Wang F., Wang G., Shen L., Wang J., Zheng B., Meng Q., Wang W., et al. Importance of a semen analysis report for determining the relationship between SCSA sperm DNA fragmentation index and assisted reproductive technology pregnancy rate. Reprod. Biol. 2020;20:460–464. doi: 10.1016/j.repbio.2019.09.002.
    1. Leach M., Aitken R.J., Sacks G. Sperm DNA fragmentation abnormalities in men from couples with a history of recurrent miscarriage. Aust. N. Z. J. Obstet. Gynaecol. 2015;55:379–383. doi: 10.1111/ajo.12373.
    1. Nguyen T.T., Trieu T.S., Tran T.O., Luong T.L.A. Evaluation of sperm DNA fragmentation index, Zinc concentration and seminal parameters from infertile men with varicocele. Andrologia. 2019;51:1–7. doi: 10.1111/and.13184.
    1. Majzoub A., Sabanegh E. Symptomatic male with subclinical varicocele found on ultrasound evaluation. Asian J. Androl. 2016;18:313–314. doi: 10.4103/1008-682X.170864.
    1. World Health Organization . WHO Laboratory Manual for the Examination and Processing of Human Semen. 5th ed. World Health Organization Press; Geneva, Switzerland: 2010.
    1. Agarwal A., Qiu E., Sharma R. Laboratory assessment of oxidative stress in semen. Arab J. Urol. 2018;16:77–86. doi: 10.1016/j.aju.2017.11.008.
    1. Alkan İ., Yüksel M., Canat H.L., Atalay H.A., Can O., Özveri H., Başar M.M. Superoxide Anion Production by the Spermatozoa of Men with Varicocele: Relationship with Varicocele Grade and Semen Parameters. World J. Mens Health. 2018;36:255. doi: 10.5534/wjmh.180028.
    1. Finelli R., Pallotti F., Cargnelutti F., Faja F., Carlini T., Rizzo F., Lenzi A., Paoli D., Lombardo F. Sperm DNA damage and cytokines in varicocele: A case-control study. Andrologia. 2021:1–6. doi: 10.1111/and.14023.
    1. Alargkof V., Kersten L., Stanislavov R., Kamenov Z., Nikolinakos P. Relationships between sperm DNA integrity and bulk semen parameters in Bulgarian patients with varicocele. Arch. Ital. Urol. Androl. 2019;91 doi: 10.4081/aiua.2019.2.125.
    1. Pallotti F., Paoli D., Carlini T., Vestri A.R., Martino G., Lenzi A., Lombardo F. Varicocele and semen quality: A retrospective case–control study of 4230 patients from a single centre. J. Endocrinol. Invest. 2018;41:185–192. doi: 10.1007/s40618-017-0713-z.
    1. Redmon J.B., Drobnis E.Z., Sparks A., Wang C., Swan S.H. Semen and reproductive hormone parameters in fertile men with and without varicocele. Andrologia. 2019;51:1–7. doi: 10.1111/and.13407.
    1. Gill K., Rosiak-Gill A., Jakubik J., Patorski L., Lukaszuk M., Piasecka M. The higher risk for sperm DNA damage in infertile men. Ginekol. Pol. 2019;90 doi: 10.5603/GP.2019.0117.
    1. Gill K., Jakubik J., Rosiak-Gill A., Kups M., Lukaszuk M., Kurpisz M., Fraczek M., Piasecka M. Utility and Predictive Value of Human Standard Semen Parameters and Sperm DNA Dispersion for Fertility Potential. Int. J. Environ. Res. Public Health. 2019;16:2004. doi: 10.3390/ijerph16112004.
    1. Jakubik-Uljasz J., Gill K., Rosiak-Gill A., Piasecka M. Relationship between sperm morphology and sperm DNA dispersion. Transl. Androl. Urol. 2020;9:405–415. doi: 10.21037/tau.2020.01.31.
    1. Agarwal A., Roychoudhury S., Sharma R., Gupta S., Majzoub A., Sabanegh E. Diagnostic application of oxidation-reduction potential assay for measurement of oxidative stress: Clinical utility in male factor infertility. Reprod. Biomed. Online. 2017;34:48–57. doi: 10.1016/j.rbmo.2016.10.008.
    1. Majzoub A., Arafa M., Mahdi M., Agarwal A., Al Said S., Al-Emadi I., El Ansari W., Alattar A., Al Rumaihi K., Elbardisi H. Oxidation–reduction potential and sperm DNA fragmentation, and their associations with sperm morphological anomalies amongst fertile and infertile men. Arab J. Urol. 2018;16:87–95. doi: 10.1016/j.aju.2017.11.014.
    1. Martin-Hidalgo D., Bragado M.J., Batista A.R., Oliveira P.F., Alves M.G. Antioxidants and male fertility: From molecular studies to clinical evidence. Antioxidants. 2019;8:89. doi: 10.3390/antiox8040089.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj