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Increases in interleukin-6 and interferon-gamma levels is progressive in immature rats with varicocele

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Abstract

Background

Pre-pubertal varicocele can result in hypotrophy of testes, progressive deterioration of Sertoli cells and spermatogonia cell number, decrease in seminiferous diameter and cause to sperm damage.

Aims

Because of detrimental time-dependent effects of varicocele, this study describes the effects of varicocele on the levels of interleukin-6 (IL-6) and interferon-gamma in serum and testis tissue, seminiferous tubules diameter, number of Sertoli and spermatogonia cells, testis and epididymis weight and volume and sperm indices in immature rats.

Methods

Thirty-six immature rats (5–6 weeks) were assigned into six groups: three sham groups and three varicocele groups. Serum, testis, and sperm samples were collected at 9, 11, and 13 weeks after induction of varicocele or sham operation to evaluate histological parameters and levels of cytokines.

Results

Varicocele significantly caused an increase in serum and testis IL-6 and interferon-gamma, compared to related sham groups and previous varicocele groups (P < 0.05). Varicocele significantly decreased Sertoli cells and spermatogonia cell number with increasing varicocele time (P < 0.05). In the evaluation of seminiferous tubules diameter, the external, internal, and epithelium diameter were decreased compared to sham-related groups and previous varicocele groups. In the all varicocele groups, all types of sperm motility decreased compared to the related sham-operated group (P < 0.05).

Conclusions

This study suggests varicocele has a detrimental, time-dependent effect on cytokines levels and decreases Sertoli cells, spermatogonia cell number, seminiferous tubules diameter, and sperm indices.

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References

  1. Schlesinger MH, Wilets IF, Nagler HM (1994) Treatment outcome after varicocelectomy. A critical analysis. Urol Clin North Am 21:517–529

    CAS  PubMed  Google Scholar 

  2. Kamal KM, Jarvi K, Zini A (2001) Microsurgical varicocelectomy in the era of assisted reproductive technology: influence of initial semen quality on pregnancy rates. Fertil Steril 75:1013–1016

    Article  CAS  PubMed  Google Scholar 

  3. Marmar JL (2001) The pathophysiology of varicoceles in the light of current molecular and genetic information. Hum Reprod Update 7:461–472

    Article  CAS  PubMed  Google Scholar 

  4. Su LM, Goldstein M, Schlegel PN (1995) The effect of varicocelectomy on serum testosterone levels in infertile men with varicoceles. J Urol 154:1752–1755

    Article  CAS  PubMed  Google Scholar 

  5. Moretti E, Cosci I, Spreafico A et al (2009) Semen characteristics and inflammatory mediators in infertile men with different clinical diagnoses. Int J Androl 32:637–646

    Article  CAS  PubMed  Google Scholar 

  6. Kikumura A, Ishikawa T, Norose K (2012) Kinetic analysis of cytokines, chemokines, chemokine receptors and adhesion molecules in murine ocular toxoplasmosis. Br J Ophthalmol 96:1259–1267

    Article  PubMed  Google Scholar 

  7. Sahin Z, Celik-Ozenci C, Akkoyunlu G et al (2006) Increased expression of interleukin-1alpha and interleukin-1beta is associated with experimental varicocele. Fertil Steril 1:1265–1275

    Article  Google Scholar 

  8. Bian SL, Jin HB, Wang SZ et al (2007) Effects of interferon-gamma and tumor necrosis factor-alpha on the fertilizing capacity of human sperm and their mechanisms. Zhonghua Nan Ke Xue 13:681–684

    CAS  PubMed  Google Scholar 

  9. Chaudhary J, Sadler-Riggleman I, Ague JM et al (2005) The helix-loop-helix inhibitor of differentiation (ID) proteins induce post-mitotic terminally differentiated Sertoli cells to re-enter the cell cycle and proliferate. Biol Reprod 72:1205–1217

    Article  CAS  PubMed  Google Scholar 

  10. Sharpe RM, McKinnell C, Kivlin C et al (2003) Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood. Reproduction 125:769–784

    Article  CAS  PubMed  Google Scholar 

  11. Skoog SJ, Roberts KP, Goldstein M et al (1997) The adolescent varicocele: what’s new with an old problem in young patients? Pediatrics 100:112–121

    Article  CAS  PubMed  Google Scholar 

  12. Yamamoto M, Hibi H, Katsuno S et al (1995) Effects of varicocelectomy on testis volume and semen parameters in adolescents: a randomized prospective study. Nagoya J Med Sci 58:127–132

    CAS  PubMed  Google Scholar 

  13. Herbenick MA, Sprott D, Stills H et al (2008) Effects of a cyclooxygenase 2 inhibitor on fracture healing in a rat model. Am J Orthop (Belle Mead NJ) 37:E133–E137

    Google Scholar 

  14. Roberts N, Puddephat MJ, McNulty V (2000) The benefit of stereology for quantitative radiology. Br J Radiol 73:679–697

    Article  CAS  PubMed  Google Scholar 

  15. Muhlfeld C, Nyengaard JR, Mayhew TM (2010) A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research. Cardiovasc Pathol Off J Soc Cardiovasc Pathol 19:65–82

    Article  Google Scholar 

  16. Charleston JS, Hansen KR, Thyer AC et al (2007) Estimating human ovarian non-growing follicle number: the application of modern stereology techniques to an old problem. Hum Reprod 22:2103–2110

    Article  PubMed  Google Scholar 

  17. Lipshultz LI (1997) Infertility. J Urol 157:847–848

    Article  CAS  PubMed  Google Scholar 

  18. Baggiolini M, Dewald B, Moser B (1997) Human chemokines: an update. Annu Rev Immunol 15:675–705

    Article  CAS  PubMed  Google Scholar 

  19. Dousset B, Hussenet F, Daudin M et al (1997) Seminal cytokine concentrations (IL-1beta, IL-2, IL-6, sR IL-2, sR IL-6), semen parameters and blood hormonal status in male infertility. Hum Reprod 12:1476–1479

    Article  CAS  PubMed  Google Scholar 

  20. Khan SA, Khan SJ, Dorrington JH (1992) Interleukin-1 stimulates deoxyribonucleic acid synthesis in immature rat Leydig cells in vitro. Endocrinology 131:1853–1857

    CAS  PubMed  Google Scholar 

  21. Jegou B, Cudicini C, Gomez E et al (1995) Interleukin-1, interleukin-6 and the germ cell-Sertoli cell cross-talk. Reprod Fertil Dev 7:723–730

    Article  CAS  PubMed  Google Scholar 

  22. Hao W, Chan IH, Liu X et al (2012) Early post-operative interleukin-6 and tumor necrosis factor-alpha levels after single-port laparoscopic varicocelectomy in children. Pediatr Surg Int 28:281–286

    Article  PubMed Central  PubMed  Google Scholar 

  23. French DB, Desai NR, Agarwal A (2008) Varicocele repair: does it still have a role in infertility treatment? Curr Opin Obstet Gynecol 20:269–274

    Article  PubMed  Google Scholar 

  24. Lampiao F, du Plessis SS (2008) TNF-alpha and IL-6 affect human sperm function by elevating nitric oxide production. Reprod Biomed Online 17:628–631

    Article  CAS  PubMed  Google Scholar 

  25. Javanmard SH, Dana N (2012) The effect of interferon gamma on endothelial cell nitric oxide production and apoptosis. Adv Biomed Res 1:69

    PubMed Central  PubMed  Google Scholar 

  26. Perez-Rodriguez R, Roncero C, Olivan AM et al (2009) Signaling mechanisms of interferon gamma induced apoptosis in chromaffin cells: involvement of nNOS, iNOS, and NFkappaB. J Neurochem 108:1083–1096

    Article  CAS  PubMed  Google Scholar 

  27. Kim JY, Han EH, Kim HG et al (2010) Bisphenol A-induced aromatase activation is mediated by cyclooxygenase-2 up-regulation in rat testicular Leydig cells. Toxicol Lett 193:200–208

    Article  CAS  PubMed  Google Scholar 

  28. Matzkin ME, Gonzalez-Calvar SI, Mayerhofer A et al (2009) Testosterone induction of prostaglandin-endoperoxide synthase 2 expression and prostaglandin F(2alpha) production in hamster Leydig cells. Reproduction 138:163–175

    Article  CAS  PubMed  Google Scholar 

  29. Walker WH, Cheng J (2005) FSH and testosterone signaling in Sertoli cells. Reproduction 130:15–28

    Article  CAS  PubMed  Google Scholar 

  30. Paick JS, Park K, Kim SW et al (2012) Increased expression of hypoxiainducible factor-1alpha and connective tissue growth factor accompanied by fibrosis in the rat testis of varicocele. Actas Urol Esp 36:282–288

    Article  CAS  PubMed  Google Scholar 

  31. Trigo RV, Bergada I, Rey R et al (2004) Altered serum profile of inhibin B, ProalphaC and anti-Mullerian hormone in prepubertal and pubertal boys with varicocele. Clin Endocrinol (Oxf) 60:758–764

    Article  CAS  Google Scholar 

  32. Agarwal A, Deepinder F, Cocuzza M et al (2007) Efficacy of varicocelectomy in improving semen parameters: new meta-analytical approach. Urology 70:532–538

    Article  PubMed  Google Scholar 

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Acknowledgment

This study was financially supported by Tehran University of Medical Sciences (Tehran, Iran).

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, Tehran University of Medical Science, Poursina Ave, Tehran, Islamic Republic of Iran

    B. Habibi, B. Seifi & H. R. Sadeghipour

  2. Department of Histology, Faculty of Medicine, Tehran University of Medical Science, Tehran, Islamic Republic of Iran

    S. M.-H. N. Mougahi

  3. Department of Molecular Biology, School of Basic Science, Mazandaran University, Mazandaran, Islamic Republic of Iran

    M. Ojaghi

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  1. B. Habibi
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  2. B. Seifi
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  3. S. M.-H. N. Mougahi
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Correspondence to H. R. Sadeghipour.

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Habibi, B., Seifi, B., Mougahi, S.MH.N. et al. Increases in interleukin-6 and interferon-gamma levels is progressive in immature rats with varicocele. Ir J Med Sci 184, 531–537 (2015). https://doi.org/10.1007/s11845-014-1167-3

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  • DOI: https://doi.org/10.1007/s11845-014-1167-3

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