trans-resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo

Abstract

We examined the effects of trans-resveratrol on male reproductive functions; ex-vivo penile erection and in-vivo sperm counts and quality. For the ex-vivo study, the relaxation effects of resveratrol on isolated New Zealand white rabbit corpus cavernosum, precontracted by phenylephrine (5×10−5 M) were measured. The in-vivo study measured reproductive organ weights, blood testosterone levels, testicular histopathology, sperm counts, as well as the epididymal sperm motility and deformity of male ICR mice given an oral dose of resveratrol (50 mg/kg) for 28 days. Resveratrol elicited a concentration-dependent relaxing effect on corpus cavernosum, leading to a median effective concentration (EC50) of 0.29 mg/mL. Repeated treatment with resveratrol (50 mg/kg) did not cause an increase in body weight, reproductive organ weight or testicular microscopic findings; however, resveratrol did elicit an increase in blood testosterone concentration, testicular sperm counts and epididymal sperm motility by 51.6%, 15.8% and 23.3%, respectively, without influence on sperm deformity. In conclusion, we propose that resveratrol has a positive effect on male reproductive function by triggering a penile erection, as well as enhancing blood testosterone levels, testicular sperm counts, and epididymal sperm motility.

This is a preview of subscription content, access via your institution.

References

  1. Akmal, M., Qadri, J. Q., Al-Waili, N. S., Thangal, S., Haq, A., and Saloom, K. Y., Improvement in human semen quality after oral supplementation of vitamin C. J. Med. Food, 9, 440–442 (2006).

    PubMed  Article  CAS  Google Scholar 

  2. Andersson, K. E. and Wagner, G, Physiology of penile erection. Physiol. Rev., 75, 191–236 (1995).

    PubMed  CAS  Google Scholar 

  3. Carreau, S., Silandre, D., Bourguiba, S., Hamden, K., Said, L., Lambard, S., Galeraud-Denis, I., and Delalande, C., Estrogens and male reproduction: a new concept. Braz. J. Med. Biol. Res. 40, 761–768 (2007).

    PubMed  Article  CAS  Google Scholar 

  4. Chen, C. K. and Pace-Asciak, C. R., Vasorelaxing activity of resveratrol and quercetin in isolated rat aorta. Gen. Pharmac., 27, 363–366 (1996).

    CAS  Google Scholar 

  5. Crowell, J. A., Korytko, P. J., Morrissey, R. L., Booth, T. D., and Levine, B. S., Resveratrol-associated renal toxicity. Toxicol. Sci., 82, 614–619 (2004).

    PubMed  Article  CAS  Google Scholar 

  6. Fouad, R., Vivien, K., and Ronald, S., Male sexual function and its disorders: physiology, pathophysiology, clinical investigation, and treatment. Endocr. Rev., 22, 342–388 (1993).

    Google Scholar 

  7. Gehm, B. D., McAndrews, J. M., Chien, P. Y., and Jameson, J. L., Resveratrol, a polyphenolic compound found in grapes and wine, is a agonist for the estrogen receptor. Proc. Natl. Acad. Sci. USA, 94, 14138–14143 (1997).

    PubMed  Article  CAS  Google Scholar 

  8. Gruenewald, D. A. and Matsumoto, A. M., Testosterone supplementation therapy for older men: potential benefits and risks. J. Am. Geriatr. Soc., 51, 101–115 (2003).

    PubMed  Article  Google Scholar 

  9. Henry, L. A. and Witt, D. M., Resveratrol: phytoestrogen effects on reproductive physiology and behavior in female rats. Horm. Behav., 41, 220–228 (2002).

    PubMed  Article  CAS  Google Scholar 

  10. Hinrichsen, M. J. and Blagaier, J. A., Evidence supporting the existence of sperm maturation in the human epididymis. J. Reprod. Fertil., 60, 291–294 (1980).

    PubMed  CAS  Article  Google Scholar 

  11. Holdcraft, R. W. and Braun, R. E., Hormonal regulation of spermatogenesis. Int. J. Androl., 27, 335–342 (2004).

    PubMed  Article  CAS  Google Scholar 

  12. Jeon, J. H., Shin, S., Park, D., Jang, J. Y., Choi, B., Kang, J.-K., Hwang, S.-Y., and Kim, J.-C., Kim, B.-Y., Kim, M. R., and Kim, Y.-B., Fermentation filtrates of Rubus coreanus relax the corpus cavernosum and increase the sperm count and motility. J. Med. Food in press (2007).

  13. Johannes, C. B., Araujo, A. B., Feldman, H. A., Derby, C. A., Kleinman, K. P., and McKinlay, J. B., Incidence of erectile dysfunction in men 40 to 69 years old; longitudinal results from the Massachusetts male aging study. J. Urol., 163, 460–463 (2000).

    PubMed  Article  CAS  Google Scholar 

  14. Jouannet, P., Wang, C., Eustache, F., Kold-Jensen, T., and Auger, J., Semen quality and male reproductive health: the controversy about human sperm concentration decline. Acta Pathol. Microbiol. Immunol. Scand., 109, 333–344 (2001).

    CAS  Google Scholar 

  15. Juan, M. E., Gonzalez-Pons, E., Munuera, T., Ballester, J., Rodriguez-Gil, J. E., and Planas, J. M., trans-Resveratrol, a naturall antioxidant from grapes, increases sperm output in healthy rats. J. Nutr., 135, 757–760 (2005).

    PubMed  CAS  Google Scholar 

  16. Kleinert, H., Wallerath, T., Euchenhofer, C., Ihrig-Biedert, I., Li, H., and Förstermann, U., Estrogens increase transcription of the human endothelial NO synthase gene: analysis of the transcription factors involved. Hypertension, 31, 582–588 (1998).

    PubMed  CAS  Google Scholar 

  17. Li, H., Wallerath, T., and Förstermann, U., Physiological mechanisms regulating the expression of endothelial-type NO synthase. Nitric oxide Biol. Chem., 7, 103–118 (2002).

    Article  CAS  Google Scholar 

  18. Padama-Nathan, H., Eardly, I., Kloner, R. A., Laties, A. M., and Montorsi, F., A 4 year update on the safety of sildenafil citrate (Viagra). Urology, 60(suppl. 2B), 67–90 (2002).

    Article  Google Scholar 

  19. Sinclair, S., Male fertility: nutritional and environmental considerations. Altern. Med. Rev., 5, 28–38 (2005).

    Google Scholar 

  20. Wallerath, T., Deckert, G., Ternes, T., Anderson, H., Li, H., Witte, K., and Förstermann, U., Resveratrol, a polyphenolic phytoalexin present in red wine, enhances expression and activity of endothelial nitric oxide synthase. Circulation, 106, 1652–1658 (2002).

    PubMed  Article  CAS  Google Scholar 

  21. Wallerath, T., Poleo, D., Li, H., and Forstermann, U., Red wine increase the expression of human endothelial nitric oxide synthase: a mechanism that may contribute to its beneficial cardiovascular effects. J. Am. College Cardiol., 41, 479–478 (2003).

    Google Scholar 

  22. Wang, Z., Chen, Y., Lavinsky, N., Hsieh, T., Ungvari, Z., and Wu, J. M., Regulation of proliferation and gene expression in cultured human aortic smooth muscle cells by resveratrol and standardized grape extracts. Biochem. Biophys. Res. Commun., 346, 367–376 (2006).

    PubMed  Article  CAS  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Yun-Bae Kim.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Shin, S., Jeon, J.H., Park, D. et al. trans-resveratrol relaxes the corpus cavernosum ex vivo and enhances testosterone levels and sperm quality in vivo. Arch. Pharm. Res. 31, 83–87 (2008). https://doi.org/10.1007/s12272-008-1124-7

Download citation

Key words

  • Resveratrol
  • Corpus cavernosum relaxation
  • Testosterone
  • Sperm counts and motility