Urology
Volume 73, Issue 3 , Pages 461-469 , March 2009

Role of Oxidative Stress in Pathogenesis of Varicocele and Infertility

Received 1 July 2008 ,Accepted 29 July 2008.

References 

  1. French DB, Desai NR, Agarwal A. Varicocele repair: Does it still have a role in infertility treatment?. Curr Opin Obstet Gynecol. 2008;20:269–274
  2. Naughton CK, Nangia AK, Agarwal A. Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001;7:473–481
  3. Skoog SJ, Roberts KP, Goldstein M, et al. The adolescent varicocele: What's new with an old problem in young patients?. Pediatrics. 1997;100:112–121
  4. Jarow JP. Effects of varicocele on male fertility. Hum Reprod Update. 2001;7:59–64
  5. Dada R, Kumar R, Shamsi MB, et al. Azoospermia factor deletions in varicocele cases with severe oligozoospermia. Indian J Med Sci. 2007;61:505–510
  6. Hurtado de Catalfo GE, Ranieri-Casilla A, Marra FA, et al. Oxidative stress biomarkers and hormonal profile in human patients undergoing varicocelectomy. Int J Androl. 2007;30:519–530
  7. Marmar JL. The pathophysiology of varicoceles in the light of current molecular and genetic information. Hum Reprod Update. 2001;7:461–472
  8. Agarwal A, Makker K, Sharma R. Clinical relevance of oxidative stress in male factor infertility: An update. Am J Reprod Immunol. 2008;59:2–11
  9. Shiraishi K, Naito K. Effects of 4-hydroxy-2-nonenal, a marker of oxidative stress, on spermatogenesis and expression of p53 protein in male infertility. J Urol. 2007;178:1012–1017
  10. Richardson I, Grotas AB, Nagler HM. Outcomes of varicocelectomy treatment: An updated critical analysis. Urol Clin North Am. 2008;35:191–209
  11. Nallella KP, Allamaneni SS, Pasqualotto FF, et al. Relationship of interleukin-6 with semen characteristics and oxidative stress in patients with varicocele. Urology. 2004;64:1010–1013
  12. Ishikawa T, Fujioka H, Ishimura T, et al. Expression of leptin and leptin receptor in the testis of fertile and infertile patients. Andrologia. 2007;39:22–27
  13. Konukoglu D, Serin O, Turhan MS. Plasma leptin and its relationship with lipid peroxidation and nitric oxide in obese female patients with or without hypertension. Arch Med Res. 2006;37:602–606
  14. Yamagishi SI, Edelstein D, Du XL, et al. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem. 2001;276:25096–25100
  15. Turkyilmaz Z, Gulen S, Sonmez K, et al. Increased nitric oxide is accompanied by lipid oxidation in adolescent varicocele. Int J Androl. 2004;27:183–187
  16. Romeo C, Ientile R, Impellizzeri P, et al. Preliminary report on nitric oxide-mediated oxidative damage in adolescent varicocele. Hum Reprod. 2003;18:26–29
  17. Akkoyunlu G, Erdogru T, Seval Y, et al. Immunolocalization of glial cell-derived neurotrophic factor (GDNF) and its receptor GFR-alpha1 in varicocele-induced rat testis. Acta Histochem. 2007;109:130–137
  18. Chen Z, Chai Y, Cao L, et al. Glial cell line-derived neurotrophic factor promotes survival and induces differentiation through the phosphatidylinositol 3-kinase and mitogen-activated protein kinase pathway respectively in PC12 cells. Neurosciences. 2001;104:593–598
  19. Benoff SH, Millan C, Hurley IR, et al. Bilateral increased apoptosis and bilateral accumulation of cadmium in infertile men with left varicocele. Hum Reprod. 2004;19:616–627
  20. Benoff S, Goodwin LO, Millan C, et al. Deletions in L-type calcium channel alpha1 subunit testicular transcripts correlate with testicular cadmium and apoptosis in infertile men with varicoceles. Fertil Steril. 2005;83:622–634
  21. Shiraishi K, Naito K. Increased expression of Leydig cell haeme oxygenase-1 preserves spermatogenesis in varicocele. Hum Reprod. 2005;20:2608–2613
  22. Romeo C, Ientile R, Santoro G, et al. Nitric oxide production is increased in the spermatic veins of adolescents with left idiopathic varicocele. J Pediatr Surg. 2001;36:389–393
  23. Chen SS, Chang LS, Wei YH. Oxidative damage to proteins and decrease of antioxidant capacity in patients with varicocele. Free Radic Biol Med. 2001;30:1328–1334
  24. Mostafa T, Anis TH, Ghazi S, et al. Reactive oxygen species and antioxidants relationship in the internal spermatic vein blood of infertile men with varicocele. Asian J Androl. 2006;8:451–454
  25. Chen SS, Huang WJ, Chang LS, et al. 8-Hydroxy-2′-deoxyguanosine in leukocyte DNA of spermatic vein as a biomarker of oxidative stress in patients with varicocele. J Urol. 2004;172:1418–1421
  26. Weese DL, Peaster ML, Himsl KK, et al. Stimulated reactive oxygen species generation in the spermatozoa of infertile men. J Urol. 1993;149:64–67
  27. Hendin BN, Kolettis PN, Sharma RK, et al. Varicocele is associated with elevated spermatozoal reactive oxygen species production and diminished seminal plasma antioxidant capacity. J Urol. 1999;161:1831–1834
  28. Sharma RK, Pasqualotto FF, Nelson DR, et al. The reactive oxygen species-total antioxidant capacity score is a new measure of oxidative stress to predict male infertility. Hum Reprod. 1999;14:2801–2807
  29. Zini A, Buckspan M, Jamal M, Jarvi K. Effect of varicocelectomy on the abnormal retention of residual cytoplasm by human spermatozoa. Hum Reprod. 1999;14:1791–1793
  30. Koksal IT, Tefekli A, Usta M, et al. The role of reactive oxygen species in testicular dysfunction associated with varicocele. BJU Int. 2000;86:549–552
  31. Pasqualotto FF, Sharma RK, Nelson DR, et al. Relationship between oxidative stress, semen characteristics, and clinical diagnosis in men undergoing infertility investigation. Fertil Steril. 2000;73:459–464
  32. Mostafa T, Anis TH, El-Nashar A, et al. Varicocelectomy reduces reactive oxygen species levels and increases antioxidant activity of seminal plasma from infertile men with varicocele. Int J Androl. 2001;24:261–265
  33. Pasqualotto FF, Sharma RK, Kobayashi H, et al. Oxidative stress in normospermic men undergoing infertility evaluation. J Androl. 2001;22:316–322
  34. Balercia G, Arnaldi G, Fazioli F, et al. Coenzyme Q10 levels in idiopathic and varicocele-associated asthenozoospermia. Andrologia. 2002;34:107–111
  35. Allamaneni SS, Naughton CK, Sharma RK, et al. 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
  36. Agarwal A, Prabakaran S, Allamaneni SS. Relationship between oxidative stress, varicocele and infertility: A meta-analysis. Reprod Biomed Online. 2006;12:630–633
  37. Cervellione RM, Cervato G, Zampieri N, et al. Effect of varicocelectomy on the plasma oxidative stress parameters. J Pediatr Surg. 2006;41:403–406
  38. Cocuzza M, Athayde KS, Agarwal A, et al. Impact of clinical varicocele and testis size on seminal reactive oxygen species levels in a fertile population: A prospective controlled study. Fertil Steril. 2008;90:1103–1108
  39. El-Karaksy A, Mostafa T, Shaeer OK, et al. Seminal mast cells in infertile asthenozoospermic males. Andrologia. 2007;39:244–247
  40. Ishikawa T, Fujioka H, Ishimura T, et al. Increased testicular 8-hydroxy-2′-deoxyguanosine in patients with varicocele. BJU Int. 2007;100:863–866
  41. Chen SS, Huang WJ, Chang LS, et al. Attenuation of oxidative stress after varicocelectomy in subfertile patients with varicocele. J Urol. 2008;179:639–642
  42. Pasqualotto FF, Sundaram A, Sharma RK, et al. Semen quality and oxidative stress scores in fertile and infertile patients with varicocele. Fertil Steril. 2008;89:602–607
  43. Ozbek E, Cekmen M, Simsek A, et al. Comparison of antioxidant enzyme activity in the internal spermatic vein and brachial veins of patients with infertile varicocele. Int Urol Nephrol. 2008;40:679–683
  44. Sakamoto Y, Ishikawa T, Kondo Y, et al. The assessment of oxidative stress in infertile patients with varicocele. BJU Int. 2008;101:623–628
  45. Shiraishi K, Naito K. Generation of 4-hydroxy-2-nonenal modified proteins in testes predicts improvement in spermatogenesis after varicocelectomy. Fertil Steril. 2006;86:233–235
  46. Koksal IT, Usta M, Orhan I, et al. Potential role of reactive oxygen species on testicular pathology associated with infertility. Asian J Androl. 2003;5:95–99
  47. Mancini A, Meucci E, Milardi D, et al. Seminal antioxidant capacity in pre- and postoperative varicocele. J Androl. 2004;25:44–49
  48. Greco E, Iacobelli M, Rienzi L, et al. Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. J Androl. 2005;26:349–353
  49. Takihara H, Cosentino MJ, Cockett AT. Zinc sulfate therapy for infertile male with or without varicocelectomy. Urology. 1987;29:638–641
  50. Yan LF, Jiang MF, Shao RY. Clinical observation on effect of jingling oral liquid in treating infertile patients with varicocele after varicocelectomy. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2004;24:220–222

 This study was supported by funds from grants 5549 and 6209 from the Cleveland Clinic and a fellowship from the American Foundation of Urological Diseases to R. K. Sharma.

PII: S0090-4295(08)01422-2

doi: 10.1016/j.urology.2008.07.053

Urology
Volume 73, Issue 3 , Pages 461-469 , March 2009

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