Reproductive and Developmental Biology

The Korean Society of Animal Reproduction (한국동물번식학회)
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Long-Term Exposure of Sildenafil Citrate on Sperm Parameters in Rat

  • Suresh, Sekar (Department of Anatomy, Dr. Arcot Lakshmanasamy Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus) ;
  • Prithiviraj, Elumali (Department of Anatomy, Dr. Arcot Lakshmanasamy Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus) ;
  • Venkatalakshmi, Nagella (Department of Anatomy, Dr. Arcot Lakshmanasamy Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus) ;
  • Ganesh, Mohanraj Karthik (Department of Anatomy, Dr. Arcot Lakshmanasamy Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus) ;
  • Ganesh, Lakshmanan (Department of Anatomy, Dr. Arcot Lakshmanasamy Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus) ;
  • Lee, Hyun-Jeong (Division of Animal Genomics and Bioinformatics, National Institute of Animal Science, Rural Development Administration) ;
  • Prakash, Seppan (Department of Anatomy, Dr. Arcot Lakshmanasamy Mudaliar Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus)
  • Received : 2011.11.05
  • Accepted : 2011.11.15
  • Published : 2011.12.31
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Abstract

Sildenafil citrate (SIL) a phosphodiesterase 5 inhibitor (PDE5I) has been used for long time as a first line oral drug for erectile dysfunction. Though it has beneficial effects on erectile organ it also has some adverse effects in other cells and/or tissues related to reproductive system when exposed to longer duration. The objective of the present study is to evaluate the long term effect of SIL on sperm parameters in Wistar albino rat. The animals are divided into two groups, for group I - rats were treated with saline (vehicle alone) and group - II oral administration of 5 mg/kg b.w. of SIL was administrated orally once in a day for 120 days. At the end of the trial period animals were sacrificed and epididymal sperm were subjected to various analysis. Results showed significant reduction in sperm count, motility, viability and morphologically intact sperm in long term PDE5I exposed animals when compared to control. Acrosomal status and fertility test also showed significant reduction in long term PDE5I exposed animals. The present study clearly indicated that long term SIL has shown to induce alteration in sperm quality and quantity, leading to decline in fertility rate. Indicate that SIL impinge on spermatogenesis as well as epididymal function. Understanding the molecular down-stream events involved in long-term exposure to PDE5 inhibitor can be valuable to supervise on related infertility issues and to suggest corrective measures.

Keywords

References

  1. Aversa A, Mazzilli F, Rossi T, Delfino M, Isidori AM, Fabbri A (2000): Effects of sildenafil (Viagra™) administration on seminal parameters and post-ejaculatory refractory time in normal males. Hum Reprod 15:131-134. https://doi.org/10.1093/humrep/15.1.131
  2. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor AM (1998): Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 159:2164-2171. https://doi.org/10.1016/S0022-5347(01)63299-3
  3. Bivalacqua TJ, Usta MF, Champion HC, Leungwattanakij S, Dabisch PA, McNamara DB, Kadowitz P J, Hellstrom WJG (2004) Effect of combination endothelial nitric oxide synthase gene therapy and sildenafil on erectile function in diabetic rats. Int J Impot Res 16: 21-29. https://doi.org/10.1038/sj.ijir.3901054
  4. Boolell M, Allen MJ, Ballard SA (1996): Oral sildenafil: an orally active type 5 cyclic GMP specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. Int J Impot Res 8:47-52.
  5. Burger M, Sikka SC, Bivalacqua TJ, Lamb DJ, Hellstrom WJ (2000): The effect of sildenafil in human sperm motion and function of normal and infertile men. Int J Impot Res 12: 229-34. https://doi.org/10.1038/sj.ijir.3900551
  6. Cooper TG (2011): The epididymis, cytoplasmic droplets and male fertility. Asi J Androl 13: 130-138. https://doi.org/10.1038/aja.2010.97
  7. Cosentino MJ, Cockett ATK (1986): Review article: structure and function of the epididymis. Urol Res 14:229-240.
  8. Eweka AO, Eweka AB (2011): The effects of sildenafil ciltrate on the medial geniculate body of adult Wistar rats (Rattus norvegicus)-A histological study. J Cell Ani Biol 5: 56-60.
  9. Fiscor G, Ginsberg LC, Oldford GM, Snoke RE, Becker RW (1983): Gelatin substrate flim techenique for detection f acrocin in single mammalian sperm. Fertil Steril 30:543-552.
  10. Glenn DRJ, McClure N, Louise Cosby S, Stevenson M, Lewis SEM (2009): Sildenafil citrate (Viagra) impairs fertilization and early embryo development in mice. Fertil Steril 91: 893-899.
  11. Glenn DRJ, McVicar CM, McClure N, Lewis SEM (2007): Sildenafil citrate improves sperm motility but causes a premature acrosome reaction in vitro. Fertil Steril 87:1064-1070. https://doi.org/10.1016/j.fertnstert.2006.11.017
  12. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA (1998) Oral sildenafil in the treatment of erectile dysfunction. Sildenafil study group. N Engl J Med 338:1397-404. https://doi.org/10.1056/NEJM199805143382001
  13. Hafez ESS (1977): Techniques of Human Andrology. Netherland: Elsevier/North-Holland Biomedical Press. 471.
  14. Kiroglu AF, Bayrakli H, Yuca K, Cankaya H, Kiris M (2006): Nasal obstraction as a common side effect of sildenafil citrate. Tohoku. J. Exp. Med 208: 251-254.
  15. Kovanecz I, Rambhatla A, Ferrini M, Vernet D, Sanchez S, Rajfer J, Gonzalez-Cadavid N (2008): Longterm continuous sildenafil treatment ameliorates corporal veno-occlusive dysfunction (CVOD) induced by cavernosal nerve resection in rats. Int J Impot Res 20:202-212. https://doi.org/10.1038/sj.ijir.3901612
  16. Mostafa T (2007) In vitro sildenafil citrate use as a sperm motility stimulant. Fertil Steril 88:994-996. https://doi.org/10.1016/j.fertnstert.2006.11.182
  17. Purvis K, Muirhead GJ, Harness JA (2002): The effects of sildenafil on human sperm function in healthy volunteers. Br J Clin Pharmacol. 53: 53S-60S. https://doi.org/10.1046/j.0306-5251.2001.00033.x
  18. Rendell MS, Rajfer J, Wicker PA, Smith MD (1999): Sildenafil for treatment of erectile dysfunction in men with diabetes. JAMA 281:421-426. https://doi.org/10.1001/jama.281.5.421
  19. Sivasankaran TG, Udayakumar R, Panjamurthy K, Albert singh V (2007): Impact of sildentfil citrate (Viagra) with ethanol modulate on lipid and lipoprotein in testis of albino rats. J Biol Scien 7:288-293. https://doi.org/10.3923/jbs.2007.288.293
  20. Suresh S, Prakash S (2010) Effect of Mucuna pruriens (Linn.) on sexual behavior and sperm parameters in streptozotocin-induced diabetic male rat. The Journal of Sexual Medicine, DOI: 10.1111/j.1743-6109. 2010.01831.x
  21. Suresh S, Prakash S (2011): Effect of Mucuna pruriens (Linn.) on oxidative stress-induced structural alteration of corpus cavernosum in streptozotocin- induced diabetic rat. J Sex Med 8:1943-1956. https://doi.org/10.1111/j.1743-6109.2011.02221.x
  22. Suresh S, Prithiviraj E, Prakash S (2009) Dose- and time-dependent effects of ethanolic extract of Mucuna pruriens Linn. seed on sexual behaviour of normal male rats. J Ethnopharmacol 22:497-501.
  23. Suresh S, Prithiviraj E, Prakash S (2010): Effect of Mucuna pruriens on oxidative stress mediated damage in aged rat sperm. Int J Androl 33:22-32. https://doi.org/10.1111/j.1365-2605.2008.00949.x
  24. Syntin P, Robaire B (2001): Sperm structural and motility changes during aging in the brown Norway rat. J Androl 22: 235-244.