International Journal of
Reproductive Biomedicine
Wed, Apr 17, 2024
[Archive]
Volume 11, Issue 10 (12-2013)
IJRM 2013, 11(10): 791-0 |
Back to browse issues page
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Niakani A, Farrokhi F, Hasanzadeh S. Decapeptyl ameliorates cyclophosphamide-induced reproductive toxicity in male Balb/C mice: histomorphometric, stereologic and hormonal evidences. IJRM 2013; 11 (10) :791-0
URL: http://ijrm.ir/article-1-352-en.html
URL: http://ijrm.ir/article-1-352-en.html
1- Department of Biology, Faculty of Science, Urmia University, Urmia, Iran
2- Department of Basic Veterinary Science, Fculty of Veterinary Medicine, Urmia University, Urmia, Iran , s.hasanzadeh@mail.urmia.ac.ir
2- Department of Basic Veterinary Science, Fculty of Veterinary Medicine, Urmia University, Urmia, Iran , s.hasanzadeh@mail.urmia.ac.ir
Abstract: (2862 Views)
Background: Gonadotropin-releasing hormone (GnRH) is a reproductive key hormone. The GnRH analogues are widely used in in vitro fertilization and treatment of sex hormone-depended cancers induced by the materials used in chemotherapeutic agents.
Objective: The aim of this study is to evaluate the effects of cyclophosphamide and decapeptyl (analogues of GnRH) on histomorphometry and stereology of testicular tissue as well as gonadotropic and gonadal hormones indices in mice.
Materials and Methods: For this study, 24 adult male Balb/C strain mice were divided in four groups; first, cyclophosphamide (65 mg/kg/body weight (BW)), second, decapeptyl (0.05 mg/kg/BW), third, decapeptyl at first, and after 10 days of cyclophosphamide injection, and control group was received same volume of sterile saline. In order to evaluate the tissue changes in testes of the mice, sections were prepared and stained with Hematoxylin-Eosine, Periodic Acid Schief's (PAS) and Oil-Red-O staining techniques.
Results: The cyclophosphamide causes histomorphologic changes in the testicular tissue; whereas such changes by decapeptyl were comparatively mild. The morphometric results revealed significant reduction in diameters of seminiferous tubules (p=0.02), and the stereological results confirmed significant differences in spermatogenesis (SI) as well as rate of tubal differentiation (TDI) indices between experimental and control groups (p=0.001). In addition, the morphometric findings proved that, there are significant decrease (p=0.001) in thicknesses of epithelia and stereologic result revealed reduction in number of cell layers in both decapeptyl and chemotherapy groups, but the decrements of these parameters were significant (p=0.02) in later group. In groups that had received cyclophosphamide, and decapeptyl alone, the LH and testosterone levels were decreased significantly (p=0.03), whereas in those that had received decapeptyl along with cyclophosphamide, the LH and FSH levels showed a decline but the level of testosterone increased.
Conclusion: These results demonstrated that, analogue of GnRH i.e., decapeptyl protect morphologic, morphometric, and stereologic alterations of the testes tissue, as well as gonadotropic and gonadal hormonal changes preceding cyclophosphamide treatment in male mice.
Objective: The aim of this study is to evaluate the effects of cyclophosphamide and decapeptyl (analogues of GnRH) on histomorphometry and stereology of testicular tissue as well as gonadotropic and gonadal hormones indices in mice.
Materials and Methods: For this study, 24 adult male Balb/C strain mice were divided in four groups; first, cyclophosphamide (65 mg/kg/body weight (BW)), second, decapeptyl (0.05 mg/kg/BW), third, decapeptyl at first, and after 10 days of cyclophosphamide injection, and control group was received same volume of sterile saline. In order to evaluate the tissue changes in testes of the mice, sections were prepared and stained with Hematoxylin-Eosine, Periodic Acid Schief's (PAS) and Oil-Red-O staining techniques.
Results: The cyclophosphamide causes histomorphologic changes in the testicular tissue; whereas such changes by decapeptyl were comparatively mild. The morphometric results revealed significant reduction in diameters of seminiferous tubules (p=0.02), and the stereological results confirmed significant differences in spermatogenesis (SI) as well as rate of tubal differentiation (TDI) indices between experimental and control groups (p=0.001). In addition, the morphometric findings proved that, there are significant decrease (p=0.001) in thicknesses of epithelia and stereologic result revealed reduction in number of cell layers in both decapeptyl and chemotherapy groups, but the decrements of these parameters were significant (p=0.02) in later group. In groups that had received cyclophosphamide, and decapeptyl alone, the LH and testosterone levels were decreased significantly (p=0.03), whereas in those that had received decapeptyl along with cyclophosphamide, the LH and FSH levels showed a decline but the level of testosterone increased.
Conclusion: These results demonstrated that, analogue of GnRH i.e., decapeptyl protect morphologic, morphometric, and stereologic alterations of the testes tissue, as well as gonadotropic and gonadal hormonal changes preceding cyclophosphamide treatment in male mice.
Type of Study: Original Article |
References
1. Clayton R. Gonadotrophin-releasing hormone: its actions and receptors. J Endocrinol 1989; 120: 11-19. [DOI:10.1677/joe.0.1200011]
2. Shupnik MA. Effects of gonadotropin-releasing hormone on rat gonadotropin gene transcription in vitro: requirement for pulsatile administration for luteinizing hormone-beta gene stimulation. Mol Endocrinol 1990; 4: 1444-1450. [DOI:10.1210/mend-4-10-1444]
3. Haisenleder DJ, Ortolano GA, Yasin M, Dalkin AC, Marshall JC. Regulation of gonadotropin subunit messenger ribonucleic acid expression by gonadotropin-releasing hormone pulse amplitude in vitro. Endocrinology 1993; 132: 1292-1296. [DOI:10.1210/endo.132.3.7679975]
4. Schally AV. Luteinizing hormone-releasing hormone analogs: their impact on the control of tumorigenesis. Peptides 1999; 20: 1247-1262. [DOI:10.1016/S0196-9781(99)00130-8]
5. Schally AV, Comaru-Schally AM, Gonzalez-Barcena D, Reissmann T, Engel J. In Endometriosis Today: Advances in Research and Practice, eds. Minaguchi H, Sugimoto O. Parthenon, Carnforth, U.K; 1997: 401-413.
6. Schally AV, Comaru-Schally AM. In Cancer Medicine, eds. Holland JF, Frei E, Bast RC, Kufe DE, Pollock RE and Weichselbaum, RR. 5th Ed. Dekker, New York; 2000: 715-729.
7. Schally AV. Gynecol LH-RH analogues: I. Their impact on reproductive medicine. Gynecol Endocrinol 1999; 13: 401-409. [DOI:10.3109/09513599909167587]
8. Cook T, Sheridan WP. Development of GnRH antagonists for prostate cancer: new approaches to treatment. Oncologist 2000; 5:162-168. [DOI:10.1634/theoncologist.5-2-162]
9. Schally AV, Halmos G, Rekasi Z, Arencibia JM. In Infertility and Reproductive Medicine Clinics of North America, ed. Devroey P. Saunders, Philadelphia; 2001: 17-44.
10. Muller U, Stahel RA .Gonadal function after MACOP-B or VACOP-B with or without dose intensification and ABMT in young patients with aggressive non-Hodgkin's lymphoma. Ann Oncol 1993; 4: 399-340. [DOI:10.1093/oxfordjournals.annonc.a058519]
11. Glaser SL. Reproductive factors in Hodgkin's disease in women a review Am. J Epidemiol 1994; 139: 237-246. [DOI:10.1093/oxfordjournals.aje.a116990]
12. Johnson DH, Linde R, Hainsworth JD, Vale W, Rivier J, Stein R, et al. Effect of a luteiruzing hormone releasing hormone agonist given dunng combination chemotherapy on post-therapy fertility in male patients with lymphoma preliminary observations. Blood 1985; 65: 832-836.
13. ShennsRJ. Gonadal dysfunction. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds). Cancer- Principles and Practice of Oncology. J.B. Lippincott Co, Philadelphia; 1993: 2395-2406.
14. Wheeler GP. Studies related to the mechanism of action of cytotoxic alkylating agents. Cancer Res 1962; 22: 651-688.
15. Glode LM, Robinson J, Gould SF. Protection from cyclophosphamide induced testicular damage with an analogue of gonadotrophin-releasing hormone. Lancet 1981; 1: 1132-1136. [DOI:10.1016/S0140-6736(81)92301-1]
16. Shalizar Jalali A, Hasanzadeh Sh, Malekinejad H. Achillea millefoliumin florescence aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis: stereological evidences. Chin J Nat Med 2012; 10: 247-254. [DOI:10.3724/SP.J.1009.2012.00247]
17. Soudamani S, Yuvaraj S, Malini T, Balasubramanian K. Exprimental diabetes has advers effects on the differentiation of ventral prostate during sexual maturation of rats. Anat Rec DiscovMol Cell Evol Biol 2005; 287:1281-1289. [DOI:10.1002/ar.a.20250]
18. Porter KL, Shetty G, Meistrich ML. Testicular dema is associated with spermatogonial arrest in irradiated rats. Endocrinol 2006; 147: 1297-1305. [DOI:10.1210/en.2005-0890]
19. Meistrich ML, Wilson G, Porter KL, Huhtaniemi I, Shetty G, Shuttlesworth GA. Restoration of spermatogenesis in dibromochloropropane (DBCP)-treated rats by hormone suppression. Toxicol Sci 2003; 76: 418-426. [DOI:10.1093/toxsci/kfg237]
20. Lee G, Luna HT. Manual of Histological Staining Methods of the Armed Forces Institute of Pathology, USA: McGraw-Hill Book Company; 1968: 158-159.
21. Collins K, Geisinger K, Wagner P, Blackburn K, Washburn L, Block S. The cytologic evaluation of lipid-laden alveolar macrophages as an indicator of aspiration pneumonia in young children. Arch Pathol Lab Med 1995; 119: 229-231.
22. Gretchen L. Animal Tissue Techniques. 4th Ed. W.H. Freeman and Company; 1979: 1-198.
23. Meistrich ML. Relationship between spermatogonial stem cell survival and testis function after cytotoxic therapy. Br J Cancer Suppl 1986; 7: 89.
24. Baker JA, Buck GM, Vena JE, Moysich KB. Fertility patterns prior to testicular cancer diagnosis. Cancer Causes Control 2005; 16: 295-299. [DOI:10.1007/s10552-004-4024-2]
25. Howell S, Shalet S. Gonadal damage from chemotherapy and radiotherapy. Endocrinol Metab Clin North Am 1998; 27: 927-943. [DOI:10.1016/S0889-8529(05)70048-7]
26. Waxman JH, Ahmed R, Smith D, Wrigley PF, Gregory W, Shalet S, et al. Failure to preserve fertility m patients with Hodgkin's disease. Cancer Chemother Pharmacol 1987; 19: 159-162. [DOI:10.1007/BF00254570]
27. Vickery BH. Comparison of the potential for therapeutic utilities with gonadotropin releasing hormone agonists and antagonists Endocrin Rev 1986; 7: 115-124. [DOI:10.1210/edrv-7-1-115]
28. Peirouvi T, Farjah G, Soleimani Rad J, Ghaffari Novin M. Vitrification induced apopto-sis in spermatozoa from fertile and subfertile men. Iran J Reprod Med 2007; 5: 117-120.
29. Nseyo UO, Huben RP, Klioze SS, Pontes JE. Protection of germinal epithelium with luteinizing hormone-releasing hormone analogue. J Urol 1985; 34: 187-190. [DOI:10.1016/S0022-5347(17)47054-6]
30. Satoh K, Ohyama K, Nakagomi Y, Ohta M, Shimura Y, Sano T, et al. Effects of growth hormone on testicular dysfunction induced by cyclophosphamide (CP) in GH-deficient rats. Endocrinol J 2002; 49: 611-619. [DOI:10.1507/endocrj.49.611]
31. Hellerstedt BA, Pienta KJ. The current state of hormonal therapy for prostate cancer. CA Cancer J Clin 2002; 52: 154-179. [DOI:10.3322/canjclin.52.3.154]
32. Brawer MK. The evolution of hormonal therapy for prostatic carcinoma. Rev Urol 2001; 3: S1-S9.
33. Tohda A, Matsumiya K, Tadokoro Y, Yomogida K, Miyagawa Y, Dohmae K, et al. Testosterone suppresses spermatogenesis in juvenile spermatogonial depletion (jsd) mice. Biol Reprod 2001; 65: 532-537. [DOI:10.1095/biolreprod65.2.532]
34. Shetty G, Weng CC, Meachem SJ, Bolden-Tiller OU, Zhang Z, Pakarinen P, et al. Both testosterone and FSH independently inhibit spermatogonial differentiation in irradiated rats. Endocrinology 2006; 147: 472-482. [DOI:10.1210/en.2005-0984]
35. Brinkworth MH. Paternal transmission of genetic damage: findinds in animals and humans. Int J Androl 2000; 23: 123-135. [DOI:10.1046/j.1365-2605.2000.00222.x]
36. Masta A, Gray PJ, Philips DR. Molecular basis of nitrogen mustard effects on transcription process: role of depurination. Nucleic Acids Res 1994; 22: 3880-3886. [DOI:10.1093/nar/22.19.3880]
37. Kenney LB, Laufer MR, Grant FD, Grier H, diller L. High risk of infertility and long term gonadal damage in males treated with high does cyclophosphamide for sacoma during childhood. Cancer 2001; 91: 613-662.
https://doi.org/10.1002/1097-0142(20010201)91:3<613::AID-CNCR1042>3.0.CO;2-R [DOI:10.1002/1097-0142(20010201)91:33.0.CO;2-R]
38. Roeser HP, Stocks AE, Smith AJ. Testicular damage due to cytotoxic drugs and recovery after cessation of therapy. Aust NZ J Med 1978; 8: 250-254. [DOI:10.1111/j.1445-5994.1978.tb04518.x]
39. Schilsky RL, Lewis BJ, Sherins RJ, Young RC. Gonadal dysfunction in patients receiving chemotherapy for cancer. Ann Intern Med 1980; 93: 109. [DOI:10.7326/0003-4819-93-1-109]
40. Meistrich ML, Finch M, da Cunha MF, Hacker U, Au WW. Damaging effects of fourteen chemotherapeutic drugs on mouse testis cells. Cancer Res 1982; 42: 122-131.
41. Klingmuller D, Schepke M, Enzweiler C, Bidlingmaier F. Hormonal responses to the new potent GnRH antagonist Cetrorelix. Acta Endocrinol 1993; 128: 15-18. [DOI:10.1530/acta.0.1280015]
42. Thomson AB, Campbell AJ, Irvine DC, Anderson RA, Kelnar CJ, Wallace WH. Semen quality and spermatozoal DNA integrity in survivors of childhood cancer: a case-control study. Lancet 2002; 360: 361-367. [DOI:10.1016/S0140-6736(02)09606-X]
43. Klein EC. Gonadal complications, Section 40. Complications of cancer and its treatment. Cancer medicine, 5th Ed. 2008; 2380-2387.
Send email to the article author
| Rights and permissions | |
 |
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
