JRI 

Effects of leuprolide acetate on the ultrastructure of germ cells in adult male mice

Vol. 8, Issue 2, / July-September 2007
(pages 111-121)

Mohammad Amin Homafar Corresponding Author
- Department of Anatomy, Faculty of Medicine, Gilan University of Medical Sciences, Gilan, Iran
Jafar Soleimanirad
- Drug applied research center, Tabriz University of Medical ٍSciences, Tabriz, Iran
Ahmad Ali Ghanbari
- Anatomy Department, Faculty of Medicine, Tabriz Medical Sciences University, Tabriz, Iran
Parvaneh Tabatabaei Nabavi
- Cellular & Molecular Research Center, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Received: 7/1/2007 Accepted: 7/1/2007 - Publisher : Avicenna Research Institute

Related Articles
in Google Scholar
in PubMed

 

Other Format
pdfFull Text (En)
pdfFull Text (Fa)
pdfAbstract (En)
pdfAbstract (Fa)
pdfePUB (En)
pdfBibTeX
pdfRefMan
pdfEndNote
xmlPMC XML
online readerPMC Reader
online readerHBIs XML

 


Abstract

Introduction: Gonadotropin hormones control spermatogenesis and any alteration in their level can influence the process and subsequently the number of germ cells. Gonadotropin-releasing hormone (GnRH) agonists suppress the pituitary-gonadal axis. The objective of this study was to investigate the ultrastructural and histological alterations in spermatogenic and spermiogenic cells following administration of a single dose of leuprolide acetate, an analogue of gonadotropin-releasing hormones. Materials & Methods: This study was done on 24 adult male 8-old week mice were used. The animals were divided in to 3 groups. The control group received no drugs but to the animals in the second and third groups 0.2ml of carboxymethyl cellulose and 7.6mg/kg of leuprolide acetate were administered respectively. All the animals were dissected five weeks after the administrations and their testes were processed for the study of germ cells and morphometric studies of seminiferous tubule parameters using transmission electron (TEM) and light microscopes (LM). The results from the five groups were compared morphologically and the data were statistically analyzed by ANOVA tests. Results: The ultrastructural study revealed that most alterations were in spermiogenic cells. The nuclei and acrosomes had been deformed in most spermatids. In some developing spermatids, there were acrosomal vesicles inside the nucleus and ectoplasmic specialization had been partially deleted in some areas. The flagella were deformed in elongated spermatids and their fibrous sheaths were discontinuous. In light microscopy, the maturity of spermatogenetic cells, based on Johnson’s testicular biopsy score, in the control, sham and experimental groups were 8.1±0.53, 8.04±0.82 and 7.01±0.57 respectively and maturation had been significantly reduced in the third group (p<0.01 ). in addition, all histometric parameters in seminiferous tubules had been decreased compared to the sham and control groups (p< 0.01). conclusion: administration of a single dose of leuprolide acetate during a spermatogenetic cycle in mice is associated with adverse effects on spermatogenesis and it is mostly associated with alterations in spermiogenesis or transformation of round spermatids into elongated spermatids.< pan>


Keywords: Spermatogenesis, GnRH, Spermiogenesis, Leuprolide acetate, Mouse, Electron microscope, Germ cells, Male infertility


To cite this article:


References

  1. Gobello C. New GnRH in canine reproduction. Anim Reprod Sci. 2007;100(1-2):1-13.   [PubMed]
  2. Chillik C, Acosta A. The role of LHRH agonists and antagonists. Reprod Biomed Online. 2001;2(2):120-28.   [PubMed]
  3. Udagawa K, Takeda M, Hosaka M, Kubota Y, Ogawa T. Recovery of spermatogenesis by high dose gonado-tropin-releasing hormone analogue treatment in rat crypt orchid testis after orchiopexy: J Urol. 2002;168 (3):1279-83.   [PubMed]
  4. Udagawa K, Ogawa T, Watanabe T, Yumura Y, Takeda M, Hosaka M. GnRH analog, leuprorelin ace-tate, promotes regeneration of rat spermatogenesis after severe chemical damage. Int J Urol. 2001;8:615-22.   [PubMed]
  5. Tunn UW, Bargelloni U, Cosciani S, Fiaccavento G, Guazzieri S, Payano F. Comparison of LH-RH ana-logue 1-month depot and 3-month depot by their hormone levels and pharmacokinetic profile in patients with advanced prostate cancer. Urol Int. 1998;60 suppl 1:9-16.   [PubMed]
  6. Berges R, Bello U. Effect of a new leuprorelin formu-lation on testosterone levels in patients with advanced prostate cancer. Curr Med Res Opin. 2006; 22(4):649-55.   [PubMed]
  7. Sartor O. Eligard: leuprolide acetate in a novel sustained-release delivery system. Urology. 2003;61(2 suppl 1):25-31.   [PubMed]
  8. Endo F, Manabe F, Takeshima H, Akaza H. Protecting apermatogonia from apoptosis induced by doxorubicin using the luteinizing hormone-releasing hormone analog Leuprorelin. Int J Urol. 2003;10:72-9.   [PubMed]
  9. Manabe F, Takeshima H, Akaza H. Protecting sperma-togenesis from damage induced by doxorubicin using the luteinizing hormone-releasing hormone agonist leu-prorelin: an image analysis study of rat experimental model. Cancer. 1997;79(5);1041-21.   [PubMed]
  10. Meistrich ML. Restoration of spermatogenesis by hor-mone treatment aftercytotoxic therapy. Acta Paediatr Scand. 1999;88:19-22.   [PubMed]
  11. Kangasniemi M, Huhtaniemi I, Meistrich ML. Failure of spermatogenesisto recover despite the presence of A spermatogonia in the irradiated LBNF1 rat. Biol Reprod. 1996;54:1200-08.   [PubMed]
  12. Glode LM, Robinson Gould SF. Protection from cyclophosphamide induced testicular damage with an analogue of gonadotropin-releasing hormone. The Lancet. 1981;(23):1132-34.   [PubMed]
  13. Ogawa T, Dobrinski I, Brinster RL. Recipient prepa-ration is critical for spermatogonial transplantation in the rat. Tissue Cell. 1999;31:461-72.   [PubMed]
  14. Dobrinski I, Ogawa T, Avarbock MR, Brinster RL. Effect of the GnRH agonist leuprolide on colonization of recipient testes by donor spermatogonial stem cells after transplantation in mice. Tissue Cell.2001;33:200-7.   [PubMed]
  15. Valiente C, Corrada Y, De La Sota PE, Galassi Gerez P, Gobello C. Effect of the GnRH antagonist, acycline, on canine testicular charachteristics. Theriogenology. 2007, In press.   [PubMed]
  16. Saratsis Ph, Ypsilantis Y, Tselkas K. Semen quality during vincristine treatment in dogs with transmissible venereal tumor. Theriogenology. 2000: 53:1185-92.   [PubMed]
  17. Yeung Ch, Weinbauer GF, Cooper TG. Effect of acute androgen withdrawal by GnRH antagonist on epidi-dymal sperm motility and morphology in the cynomol-gus monkey. J Androl. 1999;20(1):72-9.   [PubMed]
  18. Adler ID. Comparison of the duration of spermato-genesis between male rodents and humans. Mutat Res. 1996;352(1-2):169-72.   [PubMed]
  19. Cheng Yan C, Mruck DD. Cell junction dynamic in the testis: sertoli-germ cell interaction and male contra-ceptive development. Physiol Rev. 2002;82: 825-74.
  20. Bancroft JD. Theory and practice of histological tech-niques. 3rd Edition, Edited by Churchill Livingstone. 2002; London.pp:305-310.
  21. Gundersen HJ, Bagger P, Bendtsen TF, Evans SM, Korbo L, Marcussen N, et al. The new stereological tools: disector, fractionator, nucleator and point sam-pled intercepts and their use in pathological research and diagnosis. APMIS. 1998;96(10):857-81.   [PubMed]
  22. Lewis-Johnes DI, Kerrigan DD. A modified Johnsen’s count for evaluation of spermatogenesis in the rat. IRCS Med Sci. 1985;13:510-1.
  23. Mohammad-Ghasemi F, Soleimanirad J, Ghanbari AA. [A morphologic and morphometric study of adult mouse testis following different doses of busulfan administration]. J Reprod Infertil. 2006;7(1):25-37. persian.   [Abstract]
  24. Hardman JG, Limbird LE, Gilman AF. Goodman & Gilmans the pharmacological basis of therapeutics, tenth edition. Edited by McGraw Hill, Mexico. 2001; pp:1552-5.
  25. Kangasniemi M, Wilson G, Huhtaniemi I, Meistrich M. Protection against procarbazine-induced testicular damage by GnRH-agonist and anti- androgen treatment in the rat. Endocrinology. 1995;136:3677-80.
  26. Handelsman DJ, Spaliviero JA, Simpson JM, Allan CM, Singht J. Spermatogenesis without gonadotropins maintenance has a lower testosterone threshold than initiation. Endocrinology. 1999;140(9):3938-46.   [PubMed]
  27. Marshall GR, Ramaswamy S, Plant TM. Gonado-tropin-independent proliferation of the pale type A spermatogonia in the adult rhesus monkey. Biol Reprod. 2005;73(2):222-9.   [PubMed]
  28. Mclachlan RI, Wfeford NG, Kretser DM, Robertson DM. The effects of recombinant follicle-stimulating hormone on the restoration of spermatogenesis in the gonadotropin releasing hormone Immunized adult rat. Endocrinology. 1995;136(9):4035-43.   [PubMed]
  29. Meistrich ML, Shetty G. Inhibition of spermatogonial differentiation by testosterone. J Androl. 2003;24(2): 135-48.   [PubMed]
  30. Kangasniemi M, Wilson G, Parchuri N, Huhtaniemi I, Meistrich ML. Rapid protection of rat spermatogenic stem cells against procarbazine by treatment with a gonadotropin-releasing hormone antagonist (Nal-Glu) and an antiandrogen (flutamide). Endocrinology. 1995; 136:2881-8.   [PubMed]
  31. فهیمه محمد قاسمی. بررسی فراساختاری و مطالعه آپوپتوز در بیضه موشهای بالغ بدنبال درمان با بوسولفان و درمان حمایتی با انالوگ GnRH. پایان نامه دکتری تخصصی بافت شناسی. دانشکده پزشکی، دانشگاه علوم پزشکی تبریز. تابستان 1385.
  32. Gosh S, Bartke A, Grasso P, Reichert LEJR, Russel LD. Structural manifestations of the rat sertoli cells to hypophysectomy: A correlative morphometric and endocrine study. Endocrinology.1992;131(1):485-97.   [PubMed]
  33. Gosh S, Bartke A, Grasso P, Reichert LEJR. Russel LD. Structural response of the hamster sertoli cell to hypophysectomia: a correlative morphometric and endocrine study. Anat Rec. 1993;237(2):296.   [PubMed]
  34. Billing H, Furuta I, Rivier C, Tapanainen J, Parvinen M, Hsueh AJW. Apoptosis in testis germ cells: Developmental changes in gonadotropin dependence and localization to selective tubule stages. Endocrino-logy. 1995;136(1):5-12.   [PubMed]
  35. Toyama Y, Maekawa M, Yuasa S. Ectoplasmic specialization in the sertoli cell: new vistas based on genetic defects and testicular toxicology. Anat Sci Int. 2003;78(1):1-16.   [PubMed]
  36. O’Donnell L, Stanton PG, Bartles JR, Robertson DM. Sertoli cell ectoplasmic specialization in the semini-ferous epithelium of the testosterone suppressed adult rat. Biol Reprod. 2000;63:99-108.   [PubMed]
  37. Anahara R, Toyama Y, Mori C. Flutamide induces ultrastructural changes in spermatids and the ectoplas-mic specialization between the sertoli cell and sper-matids in mouse testes. Reproductive Toxicology. 2004;18:589-596.   [PubMed]
  38. Behre HM, Nashan D, Hubert W, Nieschlag E: Depot gonadotropin releasing hormone agonist blunts the androgen-induced suppression of spermatogenesis in a clinical trial of male contraception. J Clin Endocrinol Metab. 1992;74(1):84-90.   [PubMed]
  39. Haywood H, Spaliviero J, Jimenz M, King NJ, Handelsman DJ, Allan CM. Sertoli cell and germ cell development in hypogonadal mice (hpg) expressing transgenic follicle stimulating hormone alone or in combination with restosterone. Endocrinology. 2003; 144(2):509-17.   [PubMed]
  40. Toyama Y, Suzuki-Toyata F, Maekawa M, Ito CH, Toshimori K. Adverse effects of bisphenil A to sper-matogenesis in mice and rats. Arch Histol Cytol. 2004; 67(4):373-381.   [PubMed]
  41. Muffly KE, Nazian SJ, Cameron DF. Effects of follicle-stimulating hormone on the junction-related Sertoli cell cytoskeleton and daily sperm production in testosterone-treated hypophysectomized rats. Biol Reprod. 1994;51(1):158-66.   [PubMed]
  42. Sinha Hikim AP, Helue Y, Wang C, Reutrakul V, Sangsuwan R, Swerdloff RS. Post testicular aninfer-tility action of triptolide in the male rat: Evidence for severe impairement of cauda epididymal sperm ultra-structure. J Androl. 2000;21(3):431-7.   [PubMed]
  43. Huynh PN, Hikim AP, Wang C, Stefonovic K, Lue YH, Leung A, et al. Long term effects of triptolide on spermatogenesis, epididymal sperm function and fertility in male rats. J Androl. 2000;21(5):689-99.   [PubMed]

COPE
SID
NLM
AJMB
IJBMLE
IJBMLE

Home | About Us | Current Issue | Past Issues | Submit a Manuscript | Instructions for Authors | Subscribe | Search | Contact Us

"Journal of Reproduction & Infertility" is owned, published, and managed by Avicenna Research Institute .
Creative Commons License

This work is licensed under a Creative Commons Attribution –NonCommercial 4.0 International License which allows users to read, copy, distribute and make derivative works for non-commercial purposes from the material, as long as the author of the original work is cited properly.

Journal of Reproductoin and Infertility (JRI) is a member of COMMITTEE ON PUBLICATION ETHICS . Verify here .

©2024 - eISSN : 2251-676X, ISSN : 2228-5482, For any comments and questions please contact us.