World J Mens Health.  2018 Sep;36(3):255-262. 10.5534/wjmh.180028.

Superoxide Anion Production by the Spermatozoa of Men with Varicocele: Relationship with Varicocele Grade and Semen Parameters

Affiliations
  • 1Department of Urology, Okmeydanı Training and Research Hospital, University of Health Sciences, Istanbul, Turkey. iltera@hotmail.com
  • 2Department of Medical Laboratory, Vocational School of Health-Related Services, Marmara University, Istanbul, Turkey.
  • 3Department of Urology & Andrology, School of Medicine, Acibadem Mehmet Ali Aydinlar University, Istanbul, Turkey.
  • 4Department of Urology & Andrology, Memorial ÅžiÅŸli Hospital, Istanbul, Turkey.

Abstract

PURPOSE
To investigate the pathophysiological role of superoxide anion and total reactive oxygen species (ROS) production by the spermatozoa of men with varicocele and its relationship with varicocele grade and semen parameters.
MATERIALS AND METHODS
This prospective study included 34 men with grade II-III varicocele, regardless of their fertility status. The control group consisted of 13 healthy men. Semen characteristics were examined according to the 2010 World Health Organization criteria. The swim-up method was used for sperm preparation. Total ROS and superoxide anion production was assayed by luminol- and lucigenin-dependent chemiluminescence (CL), respectively.
RESULTS
The men with varicocele had significantly higher total ROS and superoxide anion levels than the healthy control subjects (2.9±0.4 relative light unit (RLU) vs. 2.4±0.1 RLU, p=0.001 for luminol-dependent CL and 2.8±0.4 RLU vs. 2.3±0.2 RLU, p=0.002 for lucigenin-dependent CL). Cases of grade III varicocele had significantly higher superoxide anion and total ROS levels than grade II cases and control subjects (p < 0.001). Superoxide anion and total ROS levels were negatively correlated with all semen parameters.
CONCLUSIONS
The superoxide anion levels produced by spermatozoa were significantly higher in varicocele patients than in control subjects. ROS production was related to increased varicocele grade, impaired semen concentration, and abnormal morphology in men with varicocele. Our findings suggest that superoxide anion overproduction may be an important step in the cascade of ROS-related damage to spermatozoa, resulting in impaired semen parameters in patients with varicocele.

Keyword

Oxidative stress; Reactive oxygen species; Spermatozoa; Superoxides; Varicocele

MeSH Terms

Fertility
Humans
Luminescence
Male
Methods
Oxidative Stress
Prospective Studies
Reactive Oxygen Species
Semen*
Spermatozoa*
Superoxides*
Varicocele*
World Health Organization
Reactive Oxygen Species
Superoxides

Figure

  • Fig. 1 Log (ROS+1) levels of patients with varicocele and the control group (mean±standard deviation) assessed using luminol- (A) and lucigenin- (B) dependent chemiluminescence. ROS: reactive oxygen species. *Significant difference with the control group (p=0.001 and p=0.002, respectively). aRelative light unit/1.0×106 spermatozoa/mL.

  • Fig. 2 Luminol- (A) and lucigenin- (B) dependent log (ROS+1) levels in patients with grade II and grade III varicocele and the control group (mean±standard deviation). ROS: reactive oxygen species. *Significant difference with the other groups (p<0.001). aRelative light unit/1.0×106 spermatozoa/mL.


Reference

1. Jarow JP, Coburn M, Sigman M. Incidence of varicoceles in men with primary and secondary infertility. Urology. 1996; 47:73–76. PMID: 8560666.
Article
2. Gorelick JI, Goldstein M. Loss of fertility in men with varicocele. Fertil Steril. 1993; 59:613–616. PMID: 8458466.
3. World Health Organization. The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. Fertil Steril. 1992; 57:1289–1293. PMID: 1601152.
4. Naughton CK, Nangia AK, Agarwal A. Varicocele and male infertility: part II: pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001; 7:473–481. PMID: 11556494.
Article
5. Agarwal A, Sharma RK, Desai NR, Prabakaran S, Tavares A, Sabanegh E. Role of oxidative stress in pathogenesis of varicocele and infertility. Urology. 2009; 73:461–469. PMID: 19167039.
Article
6. Hendin BN, Kolettis PN, Sharma RK, Thomas AJ Jr, Agarwal A. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol. 1999; 161:1831–1834. PMID: 10332447.
Article
7. Pasqualotto FF, Sharma RK, Nelson DR, Thomas AJ, Agarwal A. Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil Steril. 2000; 73:459–464. PMID: 10688996.
Article
8. de Lamirande E, Jiang H, Zini A, Kodama H, Gagnon C. Reactive oxygen species and sperm physiology. Rev Reprod. 1997; 2:48–54. PMID: 9414465.
Article
9. de Lamirande E, Gagnon C. Human sperm hyperactivation and capacitation as parts of an oxidative process. Free Radic Biol Med. 1993; 14:157–166. PMID: 8381103.
10. Aitken RJ, Irvine DS, Wu FC. Prospective analysis of spermoocyte fusion and reactive oxygen species generation as criteria for the diagnosis of infertility. Am J Obstet Gynecol. 1991; 164:542–551. PMID: 1992700.
Article
11. Barzilai A, Yamamoto K. DNA damage responses to oxidative stress. DNA Repair (Amst). 2004; 3:1109–1115. PMID: 15279799.
Article
12. Zini A, Dohle G. Are varicoceles associated with increased deoxyribonucleic acid fragmentation? Fertil Steril. 2011; 96:1283–1287. PMID: 22035729.
Article
13. Mazzilli F, Rossi T, Marchesini M, Ronconi C, Dondero F. Superoxide anion in human semen related to seminal parameters and clinical aspects. Fertil Steril. 1994; 62:862–868. PMID: 7926100.
Article
14. Chiou RK, Anderson JC, Wobig RK, Rosinsky DE, Matamoros A Jr, Chen WS, et al. Color doppler ultrasound criteria to diagnose varicoceles: correlation of a new scoring system with physical examination. Urology. 1997; 50:953–956. PMID: 9426729.
Article
15. World Health Organization. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: WHO Press;2010.
16. Cho CL, Esteves SC, Agarwal A. Novel insights into the pathophysiology of varicocele and its association with reactive oxygen species and sperm DNA fragmentation. Asian J Androl. 2016; 18:186–193. PMID: 26732105.
Article
17. Aitken RJ, Buckingham DW, West KM. Reactive oxygen species and human spermatozoa: analysis of the cellular mechanisms involved in luminol- and lucigenin-dependent chemiluminescence. J Cell Physiol. 1992; 151:466–477. PMID: 1338331.
Article
18. Mostafa T, Anis T, El Nashar A, Imam H, Osman I. Seminal plasma reactive oxygen species-antioxidants relationship with varicocele grade. Andrologia. 2012; 44:66–69. PMID: 21651600.
Article
19. Sakamoto Y, Ishikawa T, Kondo Y, Yamaguchi K, Fujisawa M. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008; 101:1547–1552. PMID: 18294306.
Article
20. Allamaneni SS, Naughton CK, Sharma RK, Thomas AJ Jr, Agarwal A. Increased seminal reactive oxygen species levels in patients with varicoceles correlate with varicocele grade but not with testis size. Fertil Steril. 2004; 82:1684–1686. PMID: 15589881.
Article
21. Cam K, Simsek F, Yuksel M, Turkeri L, Haklar G, Yalcin S, et al. The role of reactive oxygen species and apoptosis in the pathogenesis of varicocele in a rat model and efficiency of vitamin E treatment. Int J Androl. 2004; 27:228–233. PMID: 15271202.
Article
22. Jafari A, Zahmatkesh M, Sadeghipour HR, Kajbafzadeh A, Sarrafnejd A, Shahrestany T, et al. Flow cytometric evaluation of sperm superoxide anion production in rats with experimental varicocele. Urology. 2010; 75:217–222. PMID: 19616831.
Article
23. Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod. 1989; 41:183–197. PMID: 2553141.
24. Smith KA, Waypa GB, Schumacker PT. Redox signaling during hypoxia in mammalian cells. Redox Biol. 2017; 13:228–234. PMID: 28595160.
Article
25. Duranteau J, Chandel NS, Kulisz A, Shao Z, Schumacker PT. Intracellular signaling by reactive oxygen species during hypoxia in cardiomyocytes. J Biol Chem. 1998; 273:11619–11624. PMID: 9565580.
Article
26. Fernández-Agüera MC, Gao L, González-Rodríguez P, Pintado CO, Arias-Mayenco I, García-Flores P, et al. Oxygen sensing by arterial chemoreceptors depends on mitochondrial complex i signaling. Cell Metab. 2015; 22:825–837. PMID: 26437605.
Article
27. Agarwal A, Sharma R, Samanta L, Durairajanayagam D, Sabanegh E. Proteomic signatures of infertile men with clinical varicocele and their validation studies reveal mitochondrial dysfunction leading to infertility. Asian J Androl. 2016; 18:282–291. PMID: 26732106.
Article
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