Biological Trace Element Research

, Volume 154, Issue 2, pp 210–216 | Cite as

Modulation of Testicular and Whole Blood Trace Element Concentrations in Conjunction with Testosterone Release Following Kisspeptin Administration in Male Rabbits (Oryctolagus cuniculus)

  • Irfan Zia QureshiEmail author
  • Qamar Abbas


The present study investigated the role of kisspeptin-10 on reproductively significant trace elements in relation to testosterone release in male rabbits, Oryctolagus cuniculus. Groups of rabbits were exposed to single 1 μg kisspeptin dose (i.v., saphenous vein), while simultaneous groups were pretreated with a kisspeptin antagonist, peptide-234 (50 μg) 20 min before administering kisspeptin. Sequential blood sampling was done through marginal ear vein puncture at staggered time intervals: 0, 0.5, 1, 2, 4, and 24 h to determine serum testosterone. Testes and whole blood were collected at 4 and 24 h post dosage to determine trace element concentrations through atomic absorption spectrophotometry. In testes, zinc (Zn), manganese (Mn), and Fe concentrations showed significant increases at 24 h, while copper (Cu) concentration was found elevated at 4 and 24 h both (P < 0.001). In whole blood, Zn and Cu concentrations were significantly elevated at 4 and 24 h, while Mn and cobalt (Co) concentrations showed increases only at 24 h (P < 0.001). Blood iron concentration was not altered in the blood. In contrast, no change occurred in testicular Co, and chromium or nickel concentrations in either testes or blood. Compared to control and predose groups, serum testosterone levels increased gradually and peaked at 2 h (P < 0.001) post kisspeptin treatment but declined thereafter. Pretreatment with antagonist abolished all increases in trace elements and testosterone concentrations. The present study provides first evidence that reproduction- and fertility-related peptide “kisspeptin” modulates testicular and blood trace elements and that this action is likely GPR54-dependent.


Trace elements Essential minerals Kisspeptin Animal reproduction Testes Male rabbits 


  1. 1.
    Favier AE (1992) The role of zinc in reproduction: hormonal mechanism. Biol Trace Elem Res 32:363–382PubMedCrossRefGoogle Scholar
  2. 2.
    Boland MP (2003) Trace minerals in production and reproduction in dairy cattle. Adv Dairy Technol 15:319–330Google Scholar
  3. 3.
    Abbasi AA, Prasad AS, Rabbani PR (1979) Experimental zinc deficiency in man: effect on spermatogenesis. Trans Assoc Am Physicians 92:230–292Google Scholar
  4. 4.
    Aggett PJ (1985) Physiology and metabolism of essential trace elements: an outline. Clin Endocrinol Metab 14(3):513–543PubMedCrossRefGoogle Scholar
  5. 5.
    Pine M, Lee B, Dearth R, Hiney JK, Dees WL (2005) Manganese acts centrally to stimulate luteinizing hormone secretion: a potential influence on female pubertal development. Toxicol Sci 85:880–885PubMedCrossRefGoogle Scholar
  6. 6.
    Keen CL, Zidenberg-Cheer S (1990) In: Brown ML (ed) In present knowledge in nutrition. International Life science Institute Nutrition Foundation Washington DC, Manganese, pp 279–268Google Scholar
  7. 7.
    Tuormaal TE (2000) Chromium, selenium, copper and other trace minerals in health and reproduction. J Orthomol Med 15(3):145–157Google Scholar
  8. 8.
    Zini A, Schlegel PN (1997) Cu/Zn superoxide dimutase, catalase and glutahione peroxidase mRNA expression in the rat testis after surgical cryptochidism and efferent duct ligation. J Urol 158:659–663PubMedCrossRefGoogle Scholar
  9. 9.
    Michelle S, France AP, Oise B (2001) Minerals, trace elements and related biological variables in athletes and during physical activity. Clin Chem Acta 312:1–11CrossRefGoogle Scholar
  10. 10.
    Yokoi K, Uthus EO, Nielsen FH (2003) Nickel deficiency diminishes sperm quantity and movement in rats. Biol Trace Elem Res 93:141–154PubMedCrossRefGoogle Scholar
  11. 11.
    Pereira ML, Neves RP, Oliveira H, Santos TM, Jesus JP (2005) Effect of Cr(V) on reproductive organ morphology and sperm parameters: an experimental study in mice. Environ Health 4:1–6CrossRefGoogle Scholar
  12. 12.
    Anderson RA, Polansky MM (1981) Dietary chromium deficiency: effect on sperm count and fertility in rats. Biol Trace Elem Res 3:1–5CrossRefGoogle Scholar
  13. 13.
    Gottsch ML, Clifton DK, Steiner RA (2004) Galanin-like peptide as a link in the integration of metabolism and reproduction. Trends Endocrinol Metab 15:215–221PubMedCrossRefGoogle Scholar
  14. 14.
    Navarro VM, Castellano JM, Fernández-Fernández R, Barreiro ML, Roa J, Sanchez-Criado JE (2004) Developmental and hormonally regulated messenger ribonucleic acid expression of KiSS-1 and its putative receptor, GPR54, in rat hypothalamus and potent luteinizing hormone-releasing activity of KiSS-1 peptide. Endocrinol 145:4565–4574CrossRefGoogle Scholar
  15. 15.
    Kadokawa HM, Matsui K, Hayashi N, Matsunaga C, Kawashima T, Shimizu K, Kida A, Miya M (2008) Peripheral administration of kisspeptin 10 increases plasma concentrations of GH as well as LH in prepubertal Holstein heifers. J Endocrinol 196(2):331–334PubMedCrossRefGoogle Scholar
  16. 16.
    Plant TM, Ramaswamy S, Dipietro MJ (2006) Repetitive activation of hypothalamic G protein-coupled receptor 54 with intravenous pulses of kisspeptin in the juvenile monkey (Macaca mulatta) elicits a sustained train gonadotropin-releasing hormone discharge. Endocrinology 147:1007–1013PubMedCrossRefGoogle Scholar
  17. 17.
    Dhillo WS, Chaudri OB, Patterson M, El T, Murphy KG, Badman MK, McGowan BM, Amber V, Patel S, Ghatei MA (2005) kisspeptin-54 stimulates the hypothalamic–pituitary–gonadal axis in human males. J Clin Endocrinol Metab 90:6609–6615PubMedCrossRefGoogle Scholar
  18. 18.
    Hameed S, Jayasena CN, Dhillo WS (2011) Kisspeptin and fertility. J Endocrinol 208:97–105PubMedCrossRefGoogle Scholar
  19. 19.
    Tena-Sempere M, Felip A, Gomez A, Zanuy S, Carrilo M (2012) Comparative insights of the kisspeptin/kisspeptin receptor system: from non mammalian vertebrates. Gen Comp Endocrinol 175:234–243PubMedCrossRefGoogle Scholar
  20. 20.
    Lee JH, Miele ME, Hicks DJ, Phillips JJ, Trent JM, Weissman BE, Welch DR (1996) KiSS-1, a novel human malignant melanoma metastasis-suppressor gene. J Natl Cancer Inst 88:1731–1737PubMedCrossRefGoogle Scholar
  21. 21.
    Kirby HR, Maguire JJ, Colledge WH, Davenport AP (2010) International Union of Basic and Clinical Pharmacology. LXXVII. Kisspeptin receptor nomenclature, distribution, and function. Pharmacol Rev 62:565–578PubMedCrossRefGoogle Scholar
  22. 22.
    Reynolds RM, Logie JJ, Rosewier AK, McKnight AJ, Miller RP (2009) A role for kisspeptin in pregnancy: facts and speculations. Reproduction 138:1–7PubMedCrossRefGoogle Scholar
  23. 23.
    Mapara M, Thomas BS, Bhat KM (2012) Rabbit as an animal model for experimental research. Dent Res J (Isfahan) 9(1):111–118CrossRefGoogle Scholar
  24. 24.
    Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, Ghatei MA, Bloom SR (2004) Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic–pituitary–gonadal axis. J Neuroendocrinol 16(10):850–858PubMedCrossRefGoogle Scholar
  25. 25.
    Jens DM, Agnete HB, Laura A, Valerie S, Anders J (2009) Comparison of the effects of peripherally administered kisspeptins. Regul Pept 152:95–100CrossRefGoogle Scholar
  26. 26.
    Yousofvand N, Zarei F, Ghanbari A (2013) Exogenous testosterone, finasteride and castration effects on testosterone, insulin, zinc and chromium in adult male rats. Iranian Biomed J 17(1):49–53Google Scholar
  27. 27.
    Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, Terao Y, Kumano S, Takatsu Y, Masuda Y, Ishibashi Y, Watanabe T, Asada M, Yamada T, Suenaga M, Kitada C, Usuki S, Kurokawa T, Onda H, Nishimura O, Fujino M (2001) Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 411(6837):613–617PubMedCrossRefGoogle Scholar
  28. 28.
    Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, Brézillon S, Tyldesley R, Suarez-Huerta N, Vandeput F, Blanpain C, Schiffmann SN, Vassart G, Parmentier M (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan G protein-coupled receptor GPR54. J Biol Chem 276(37):34631–34636PubMedCrossRefGoogle Scholar
  29. 29.
    Ramzan F, Qureshi IZ (2011) Intraperitoneal kisspeptin-10 administration induces dose-dependent degenerative changes in maturing rat testes. Life Sci 88(5–6):246–256PubMedCrossRefGoogle Scholar
  30. 30.
    Marzec-Wroblewska U, Kaminski P, Lakota P (2012) Influence of chemical elements on mammalian spermatozoa. Folia Biol (Praha) 58:7–15Google Scholar
  31. 31.
    Agarwal A, Prabakaran SA (2005) Oxidative stress and antioxidants in male infertility: a difficult balance. Iranian J Rep Med 3(1):1–8Google Scholar
  32. 32.
    Bansal AK, Bilaspuri GS (2011) Impacts of oxidative stress and antioxidants on semen functions. Vet Med Intern SAGE-Hindawi : 1–7Google Scholar
  33. 33.
    Nordberg J, Arnere SJ (2001) Reactive oxygen species, antioxidants, and the mammalian thioredoxin system. Free Radic Biol Med 31(11):1287–1312PubMedCrossRefGoogle Scholar
  34. 34.
    Hamdi SA, Nassif OI, Ardawi MS (1997) Effects of marginal or severe dietary zinc deficiency on testicular development and function of the rat. Arch Androl 38(3):243–253PubMedCrossRefGoogle Scholar
  35. 35.
    Powell SR (2000) The antioxidant properties of zinc. J Nutr 130:1447S–1454SPubMedGoogle Scholar
  36. 36.
    Apgar J (1985) Zinc and reproduction. Annu Rev Nutr 5:43–68PubMedCrossRefGoogle Scholar
  37. 37.
    Cigankova V, Mesaros P, Bires J, Ledecky V, Ciganek J, Tomajkova E (1998) The morphological structure of the testis in stallions with zinc deficiency. Slov Vet 23:97–100 (in Slovak)Google Scholar
  38. 38.
    Krupej J, Tomala J, Zych F, Bakon I, Orgacka H, Machalski T (1994) Zinc levels in semen of men from childless marriages. Ginekol Pol 65:239–243PubMedGoogle Scholar
  39. 39.
    Bianchi F, Rousseaux-Prevost R, Sautiere P, Rousseaux J (1992) P2 protamines from human sperm are zinc-finger proteins with one CYS2/HIS 2 motif. Biochem Biophys Res Commun 182:540–547PubMedCrossRefGoogle Scholar
  40. 40.
    Colagar AH, Marzony ET, Chaichi MJ (2009) Zinc levels in seminal plasma are associated with sperm quality in fertile and infertile men. Nutr Res 29(2):82–88PubMedCrossRefGoogle Scholar
  41. 41.
    Sørensen MB, Stoltenberg M, Danscher G, Ernst E (1999) Chelating of intracellular zinc ions affects human sperm cell motility. Mol Hum Reprod 5:338–341PubMedCrossRefGoogle Scholar
  42. 42.
    Dissanayake DM, Wijesinghe PS, Ratnasooriya WD, Wimalasena S (2010) Relationship between seminal plasma zinc and semen quality in a subfertile population. J Hum Reprod Sci 3(3):124–128PubMedCrossRefGoogle Scholar
  43. 43.
    Cheema RS, Bansal AK, Bilaspuri GS (2009) Manganese provides antioxidant protection for sperm cryopreservation that may offer new consideration for clinical fertility. Oxid Med Cell Longev 2(3):152–159PubMedCrossRefGoogle Scholar
  44. 44.
    Gavella M, Lipovac V (1988) In vitro effect of zinc on oxidative changes in human semen. Andrologia 30:317–323CrossRefGoogle Scholar
  45. 45.
    Kabata-Pendias A, Mukherjee AB (2007) Trace elements from soil to human. Springer, HeidelbergCrossRefGoogle Scholar
  46. 46.
    Barceloux D (1999) Cobalt. Clin Toxicol 37:201–216CrossRefGoogle Scholar
  47. 47.
    Kodentsova VM, Vrzesinskaya OA, Spirichev VB (1994) Male fertility: a possible role of vitamins. Ukr Biokhim Zh 66(5):17–22PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Laboratory of Animal and Human Physiology, Department of Animal Sciences, Faculty of Biological SciencesQuaid-i-Azam UniversityIslamabadPakistan

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