Skip to main content
SpringerLink
Log in

Green tea extracts attenuate doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity in mice

  • fertility preservation
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to investigate the protective effect of green tea extracts against doxorubicin-induced damage in the mouse testes correlating with telomerase activity.

Methods

Green tea extracts were administered orally. Doxorubicin was coadministered intraperitoneally. These testes were evaluated histologically and the telomerase activity was analyzed. Additional immunostaining was carried out.

Results

Both the sperm density and sperm motility were significantly increased in green tea extracts coadministration groups as compared to the doxorubicin-treated groups. By histological analysis, germ cell damage was greatly attenuated by green tea extracts coadministration. Telomerase activity significantly increased in association with the coadministration of green tea extracts as compared to that of doxorubicin-only groups. In all groups, human telomerase reverse transcriptase signals were mainly observed in the spermatocytes and spermatids.

Conclusions

These findings suggest that green tea extracts exert protective effects against doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity levels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Mukhtar H, Ahmad N. Green tea in chemoprevention of cancer. Toxicol Sci. 1995;52:111–7.

    Google Scholar 

  2. Clement Y. Can green tea do that? A literature review of the clinical evidence. Prev Med. 2009;49:83–7.

    Article  PubMed  Google Scholar 

  3. Schneider C, Segre T. Green tea: potential health benefits. Am Fam Physician. 2009;79:591–4.

    PubMed  Google Scholar 

  4. Valcic S, Muders A, Jacobsen NE, Liebler DC, Timmermann BN. Antioxidant chemistry of green tea catechins. Identification of products of the reaction of (−)-epigallocatechin gallate with peroxyl radicals. Chem Res Toxicol. 1999;12:382–6.

    Article  CAS  PubMed  Google Scholar 

  5. Rice-Evans C. Plant polyphenols: free radical scavengers or chain-breaking antioxidants? Biochem Soc Symp. 1995;61:103–16.

    CAS  PubMed  Google Scholar 

  6. Salah N, Miller NJ, Paganga G, Tijburg L, Bolwell GP, Rice-Evans C. Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants. Arch Biochem Biophys. 1995;322:339–46.

    Article  CAS  PubMed  Google Scholar 

  7. Sung H, Nah J, Chun S, Park H, Yang SE, Min WK. In vivo antioxidant effect of green tea. Eur J Clin Nutr. 2000;54:527–9.

    Article  CAS  PubMed  Google Scholar 

  8. Rietveld A, Wiseman S. Antioxidant effects of tea: evidence from human clinical trials. Nutr. 2003;133:3285S–92.

    CAS  Google Scholar 

  9. Nakagawa K, Ninomiya M, Okubo T, Aoi N, Juneja LR, Kim M, et al. Tea catechin supplementation increases antioxidant capacity and prevents phospholipids hydroperoxidation in plasma of humans. J Agri Food Chem. 1999;47:3967–73.

    Article  CAS  Google Scholar 

  10. Di Marco A, Gaetani M, Scarpinato B. Adriamycin (NSC-123, 127): a new antibiotic with antitumor activity. Cancer Chemother Rep. 1969;53:33–7.

    PubMed  Google Scholar 

  11. Quiles JL, Huertas JR, Battino M, Mataix J, Ramirez-Tortosa MC. Antioxidant nutrients and adriamycin toxicity. Toxicology. 2002;30:79–95.

    Article  Google Scholar 

  12. Imahie H, Adachi T, Nakagawa Y, Nagasaki T, Yamamura T, Hori M. Effects of adriamycin, an anticancer drug showing testicular toxicity, on fertility in male rats. J Toxicol Sci. 1995;20:183–93.

    CAS  PubMed  Google Scholar 

  13. Lui RC, Laregina MC, Herbold DR, Johnson FE. Testicular cytotoxicity of intravenous doxorubicin in rats. J Urol. 1986;136:940–3.

    CAS  PubMed  Google Scholar 

  14. Dorr RT. Cytoprotective agents for anthracyclines. Semin Oncol. 1996;23:23–34.

    CAS  PubMed  Google Scholar 

  15. Herman EH, Zhang J, Chadwick DP, Ferrans VJ. Comparison of the protective effects of amifostine and dexrazoxane against the toxicity of doxorubicin in spontaneously hypertensive rats. Cancer Chemother Pharmacol. 2000;45:329–34.

    Article  CAS  PubMed  Google Scholar 

  16. Wattanapitayakul SK, Chularojmontri L, Herunsalee A, Charuchongkolwongse S, Niumsakul S, Bauer JA. Screening of antioxidants from medicinal plants for cardioprotective effect against doxorubicin toxicity. Basic Clin Pharmacol Toxicol. 2005;96:80–7.

    Article  CAS  PubMed  Google Scholar 

  17. Prowse KR, Greider CW. Developmental and tissue-specific regulation of mouse telomerase and telomere length. Proc Natl Acad Sci USA. 1995;92:4818–22.

    Article  CAS  PubMed  Google Scholar 

  18. Kim NW, Piatyszek MA, Prowse KR, Harley CB, West MD, Ho PL, et al. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994;266:2011–5.

    Article  CAS  PubMed  Google Scholar 

  19. Weise JM, Güneş C. Differential regulation of human and mouse telomerase reverse transcriptase (TERT) promoter activity during testis development. Mol Reprod Dev. 2009;76:309–17.

    Article  CAS  PubMed  Google Scholar 

  20. Coussens M, Yamazaki Y, Moisyadi S, Suganuma R, Yanagimachi R, Allsopp R. Regulation and effects of modulation of telomerase reverse transcriptase expression in primordial germ cells during development. Biol Reprod. 2006;75:785–91.

    Article  CAS  PubMed  Google Scholar 

  21. Fajkus J, Dvorácková M, Sýkorová E. Analysis of telomeres and telomerase. Meth Mol Biol. 2008;463:267–96.

    Article  CAS  Google Scholar 

  22. Zalenskaya IA, Zalensky AO. Telomeres in mammalian male germline cells. Int Rev Cytol. 2002;218:37–67.

    Article  CAS  PubMed  Google Scholar 

  23. Eisenhauer KM, Gerstein RM, Chiu CP, Conti M, Hsueh AJ. Telomerase activity in female and male rat germ cells undergoing meiosis and in early embryos. Biol Reprod. 1997;56:1120–5.

    Article  CAS  PubMed  Google Scholar 

  24. Yamamoto Y, Sofikitis N, Ono K, Kaki T, Isoyama T, Suzuki N, et al. Postmeiotic modifications of spermatogenic cells are accompanied by inhibition of telomerase activity. Urol Res. 1999;27:336–45.

    Article  CAS  PubMed  Google Scholar 

  25. Achi MV, Ravindranath N, Dym M. Telomere length in male germ cells is inversely correlated with telomerase activity. Biol Reprod. 2000;63:591–8.

    Article  CAS  PubMed  Google Scholar 

  26. Hisatomi H, Nagao K, Komatsu H. Quantification of telomerase activity in human liver tissues by fluorescence based TRAP analysis. Hepat Res. 1997;7:35–42.

    Article  Google Scholar 

  27. Ohyashiki JH, Ohyashiki K, Toyama K, Shay JW. A nonradioactive, fluorescence-based telomeric repeat amplification protocol to detect and quantitate telomerase activity. Trends Genet. 1996;12:395–6.

    Article  CAS  Google Scholar 

  28. Ateşşahin A, Türk G, Karahan I, Yilmaz S, Ceribaşi AO, Bulmuş O. Lycopene prevents adriamycin-induced testicular toxicity in rats. Fertil Steril. 2006;85 Suppl 1:1216–22.

    PubMed  Google Scholar 

  29. Kang J, Lee Y, No K, Jung E, Sung J, Kim Y, et al. Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis. Reprod Toxicol. 2002;16:291–8.

    Article  CAS  PubMed  Google Scholar 

  30. Kyo S, Masutomi K, Maida Y, Kanaya T, Yatabe N, Nakamura M, et al. Significance of immunological detection of human telomerase reverse transcriptase: re-evaluation of expression and localization of human telomerase reverse transcriptase. Am J Pathol. 2003;163:859–67.

    CAS  PubMed  Google Scholar 

  31. Kagaya N, Tagawa Y, Nagashima H, Saijo R, Kawase M, Yagi K. Suppression of cytotoxin-induced cell death in isolated hepatocytes by tea catechins. Eur J Pharmacol. 2002;450:231–6.

    Article  CAS  PubMed  Google Scholar 

  32. Hisano M, Yamaguchi K, Inoue Y, Ikeda Y, Iijima M, Adachi M, et al. Inhibitory effect of catechin against the superantigen staphylococcal enterotoxin B (SEB). Arch Dermatol Res. 2003;295:183–9.

    Article  CAS  PubMed  Google Scholar 

  33. Raihan SZ, Chowdhury AK, Rabbani GH, Marni F, Ali MS, Nahar L, et al. Effect of aqueous extracts of black and green teas in arsenic-induced toxicity in rabbits. Phytother Res. 2009;23:1603–8.

    Article  CAS  PubMed  Google Scholar 

  34. Chen X, Sun CK, Han GZ, Peng JY, Li Y, Liu YX, et al. Protective effect of tea polyphenols against paracetamol-induced hepatotoxicity in mice is significantly correlated with cytochrome P450 suppression. World J Gastroenterol. 2009;15:1829–35.

    Article  CAS  PubMed  Google Scholar 

  35. Shin BC, Ryu HH, Chung JH, Lee BR, Kim HL. The protective effects of green tea extract against L-arginine toxicity to cultured human mesangial cells. J Korean Med Sci. 2009;24(Suppl):S204–9.

    Article  PubMed  Google Scholar 

  36. Fadhel ZA, Amran S. Effects of black tea extract on carbon tetrachloride-induced lipid peroxidation in liver, kidneys, and testes of rats. Phytother Res. 2002;16:S28–32.

    Article  PubMed  Google Scholar 

  37. Ozdemir S, Dursun S. Role of + (−)catechin against cadmium toxicity in the rat testes. Scand J Urol Nephrol. 2008;23:1–4.

    Google Scholar 

  38. Sudo K. An experimental model of adriamycin-induced spermatogenic disorder in mice (1): histological and functional analysis. J Med Soc Toho. 1991;38:462–75. Japanese.

    CAS  Google Scholar 

  39. Lu CC, Meistrich ML. Cytotoxic effects of chemotherapeutic drugs on mouse testis cells. Cancer Res. 1979;39:3575–82.

    CAS  PubMed  Google Scholar 

  40. Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl. 2008;29:488–98.

    Article  CAS  PubMed  Google Scholar 

  41. Mandal TK, Das NS. Effect of delta-9-tetrahydrocannabinol on altered antioxidative enzyme defense mechanisms and lipid peroxidation in mice testes. Eur J Pharmacol. 2009;607:178–87.

    Article  CAS  PubMed  Google Scholar 

  42. Tavares DC, Cecchi AO, Antunes LM, Takahashi CS. Protective effects of the amino acid glutamine and of ascorbic acid against chromosomal damage induced by doxorubicin in mammalian cells. Teratog Carcinog Mutagen. 1998;18:153–61.

    Article  CAS  PubMed  Google Scholar 

  43. Balercia G, Mosca F, Mantero F, Boscaro M, Mancini A, Ricciardo-Lamonica G, et al. Coenzyme Q(10) supplementation in infertile men with idiopathic asthenozoospermia: an open, uncontrolled pilot study. Fertil Steril. 2004;81:93–8.

    Article  CAS  PubMed  Google Scholar 

  44. Agarwal A, Sharma RK, Nallella KP, Thomas Jr AJ, Alvarez JG, Sikka SC. Reactive oxygen species as an independent marker of male factor infertility. Fertil Steril. 2006;86:878–85.

    Article  CAS  PubMed  Google Scholar 

  45. Hou M, Chrysis D, Nurmio M, Parvinen M, Eksborg S, Söder O, et al. Doxorubicin induces apoptosis in germ line stem cells in the immature rat testis and amifostine cannot protect against this cytotoxicity. Cancer Res. 2005;65:9999–10005.

    Article  CAS  PubMed  Google Scholar 

  46. Miller RG, Phillips RA. Separation of cells by velocity sedimentation. J Cell Physiol. 1969;73:191–201.

    Article  CAS  PubMed  Google Scholar 

  47. Tanemura K, Ogura A, Cheong C, Gotoh H, Matsumoto K, Sato E, et al. Dynamic rearrangement of telomeres during spermatogenesis in mice. Dev Biol. 2005;281:196–207.

    Article  CAS  PubMed  Google Scholar 

  48. Liu L, Blasco M, Trimarchi J, Keefe D. An essential role for functional telomeres in mouse germ cells during fertilization and early development. Dev Biol. 2002;249:74–84.

    Article  CAS  PubMed  Google Scholar 

  49. Lee HW, Blasco MA, Gottlieb GJ, Horner 2nd JW, Greider CW, DePinho RA. Essential role of mouse telomerase in highly proliferative organs. Nature. 1998;392:569–74.

    Article  CAS  PubMed  Google Scholar 

  50. Niida H, Shinkai Y, Hande MP, Matsumoto T, Takehara S, Tachibana M, et al. Telomere maintenance in telomerase-deficient mouse embryonic stem cells: characterization of an amplified telomeric DNA. Mol Cell Biol. 2000;20:4115–27.

    Article  CAS  PubMed  Google Scholar 

  51. Reddel RR. Alternative lengthening of telomeres, telomerase, and cancer. Cancer Lett. 2003;194:155–62.

    Article  CAS  PubMed  Google Scholar 

  52. Crespy V, Williamson G. A review of the health effects of green tea catechins in in vivo animal models. J Nutr. 2004;134:3431S–40.

    CAS  PubMed  Google Scholar 

  53. Yamaguchi Y, Hayashi M, Yamazoe H, Kunitomo M. Preventive effects of green tea extract on lipid abnormalities in serum, liver and aorta of mice fed a atherogenic diet. Nippon Yakurigaku Zasshi. 1991;97:329–37.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We wish to acknowledge Ms. Hiroko Ueno and Ms. Kimiko Tokizawa for their excellent laboratory assistance, Taiyo Kagaku Co. Ltd. for their generous donation of green tea extract.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-0016, Japan

    Kenji Sato, Kou Sueoka, Reiko Tanigaki, Hiroto Tajima, Akira Nakabayashi & Yasunori Yoshimura

  2. Graduate School of Biology-Oriented Science and Technology, Kinki University, Nishimitani, Kinokawa, Wakayama, 649-6493, Japan

    Yoshihiko Hosoi

Authors
  1. Kenji Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kou Sueoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reiko Tanigaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroto Tajima
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Akira Nakabayashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yasunori Yoshimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yoshihiko Hosoi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kou Sueoka.

Additional information

Capsule

Green tea extracts may be protective against DXR-induced testicular toxicity associated with an increase in telomerase activity.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sato, K., Sueoka, K., Tanigaki, R. et al. Green tea extracts attenuate doxorubicin-induced spermatogenic disorders in conjunction with higher telomerase activity in mice. J Assist Reprod Genet 27, 501–508 (2010). https://doi.org/10.1007/s10815-010-9438-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-010-9438-z

Keywords

Search

Navigation