Skip to main content
SpringerLink
Log in

Possible Effects of Metallosis on Spermatozoal Apoptotic Genes Expression in Individuals with Intramedullary Nailing Prosthesis

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Seminal quality could be affected by metallosis caused by intramedullary nailing (IMN). Our objectives were to estimate metal ion levels in the seminal plasma of subjects with IMN, to determine their effects on semen parameters and on spermatozoal apoptotic gene expression, and to determine whether these expressed genes could be used as candidate biomarkers of seminal deterioration in individuals with IMN or not. Semen samples were collected from 60 subjects with IMN and 30 age-matched healthy controls. Seminal plasma contents of cobalt (Co), chromium (Cr), and molybdenum (Mo) were assayed. Spermatozoal Bcl-2 and Bax gene expressions were determined. Studied semen parameters were significantly lower in subjects with IMN for ≥5 years in relation to controls while the concentrations of Co, Cr, and Mo in the seminal plasma samples were significantly higher. There were significantly lower spermatozoal Bcl-2 expression, higher Bax expression, and lower Bcl-2/Bax ratio in subjects with IMN for ≥5 years than in controls. In subjects with IMN for ≥5 years, receiver operating characteristic (ROC) curve analysis of studied gene expressions and Bcl-2/Bax ratio were done showing priority of the ratio with 86.7 % sensitivity, 100 % specificity, 100 % positive predictive value, and 93.8 % negative predictive value at cutoff values ≤0.777. Co, Cr, and Mo metals are found at high concentrations in the seminal plasma of individuals with IMN leading to increased spermatozoal apoptotic activity. Spermatozoal Bcl-2/Bax ratio could be used as a candidate biomarker of reproductive disorders in individuals with intramedullary nailing.

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

Similar content being viewed by others

Abbreviations

Co:

Cobalt

Cr:

Chromium

FSH:

Follicular stimulating hormone

IMN:

Intramedullary nailing

Mo:

Molybdenum

ROC:

Receiver operating characteristic

References

  1. Telisman S, Colak B, Pizent A, Jurasovic J, Cvitkovic P (2007) Reproductive toxicity of low-level lead exposure in men. Environ Res 105(2):256–266

    Article  CAS  PubMed  Google Scholar 

  2. Jacobs JJ, Gilbert JL, Urban RM (1998) Current concepts review. Corrosion of metal orthopaedic implants. J Bone Joint Surg Am 80(2):268–282

    CAS  PubMed  Google Scholar 

  3. Patton M, Lyon T, Ashcroft G (2008) Levels of systemic metal ions in patients with intramedullary nails. Acta Orthop 79(6):820–825

    Article  PubMed  Google Scholar 

  4. Said TM, Ranga G, Agarwal A (2005) Relationship between semen quality and tobacco chewing in men undergoing infertility evaluation. Fertil Steril 84(3):649–653

    Article  PubMed  Google Scholar 

  5. Apostoli P, Catalani S (2001) Metal ions affecting reproduction and development. Met Ions Life Sci 8:263–303

    Google Scholar 

  6. Basu A, Haldar S (1998) The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death. Mol Hum Reprod 4(12):1099–1109

    Article  CAS  PubMed  Google Scholar 

  7. Youle RJ, Strasser A (2008) The BCL-2 protein family: opposing activities that mediate cell death. Nat Rev Mol Cell Bio 9(1):47–59

    Article  CAS  Google Scholar 

  8. Angelucci C, Iacopino F, Lama G, Zelano G, Gianesini G, Sica G, Bono AV (2005) Reverse transcriptase-PCR analysis of apoptosis-regulating gene expression in human benign prostatic hyperplasia. Anticancer Res 25(6B):3937–3941

    CAS  PubMed  Google Scholar 

  9. Nikolaou VS, Petit A, Debiparshad K, Huk OL, Zukor DJ, Antoniou J (2011) Metal-on-metal total hip arthroplasty—five- to 11-year follow-up. Bull NYU Hosp Jt Dis 69(Suppl 1):S77–S83

    PubMed  Google Scholar 

  10. Hinting A, Schoonjans F, Comhaire F (1988) Validation of a single-step procedure for the objective assessment of sperm motility characteristics. Int J Androl 11(4):277–287

    Article  CAS  PubMed  Google Scholar 

  11. WHO (World Health Organization) (2010) WHO laboratory manual for the examination and processing of human semen, 5th ed

  12. Endtz AW (1974) A rapid staining method for differentiating granulocytes from “germinal cells” in Papanicolaou-stained semen. Acta Cytol 18:2–7

    CAS  PubMed  Google Scholar 

  13. Sarada A, Ramasastri BV (1983) A simple thin layer chromatographic identification of choline in human semen. J Forensic Sci Soc 23(3):233–236

    Article  CAS  PubMed  Google Scholar 

  14. Raha S, Ling M, Merante F (1998) Extraction of total RNA from tissues and cultured cells. In: Rapley R, Walker JM (eds) Molecular biomethods handbook. Humana Press Inc, Totowa, pp 1–8, Ch. 1

    Chapter  Google Scholar 

  15. McPherson MJ, Moller SG (2000) Analysis of gene expression. In: McPherson MJ, Moller SG (eds) PCR, BIOS Scientific Publishers Ltd, vol 8, Oxford. Ch., pp 183–211

    Google Scholar 

  16. Liu HC, He HY, MeleCA VLL, Davis O, Rosenwaks Z (2000) Expression of apoptosis-related genes in human oocytes and embryos. J Ass Reprod Gen 17(9):521–533

    Article  CAS  Google Scholar 

  17. Zumárraga M, Andía I, Dávila R, Miller JC, Friedhoff AJ (2004) Expression in normals and in subjects with schizophrenia of a novel gene fragment originally isolated from monozygotic twins discordant for schizophrenia. Genet Mol Biol 27(1):17–21

    Article  Google Scholar 

  18. Pizent A, Tariba B, Zivkovic T (2012) Reproductive toxicity of metals in men. Arh Hig Rada Toksikol 63(Supp 1):35–46

    PubMed  Google Scholar 

  19. Mangelsdorf I, Buschmann J, Orthen B (2003) Some aspects relating to the evaluation of the effects of chemicals on male fertility. Regul Toxicol Pharmacol 37(3):356–369

    Article  CAS  PubMed  Google Scholar 

  20. Apostoli P, Telišman S, Sager PR (2007) Reproductive and developmental toxicity of metals. In: Nordberg GF, Fowler BA, Nordberg M, Friberg LT (eds) Handbook on the Toxicology of Metals, vol 7, Amsterdam: Academic Press Elsevier; Ch., pp 213–249

    Chapter  Google Scholar 

  21. Wirth JJ, Mijal RS (2010) Adverse effects of low level heavy metal exposure on male reproductive function. Syst Biol Reprod Med 56(2):147–167

    Article  CAS  PubMed  Google Scholar 

  22. Meeker JD, Rossano MG, Protas B, Diamond MP, Puscheck E, Daly D, Paneth N, Wirth JJ (2008) Cadmium, lead, and other metals in relation to semen quality: human evidence for molybdenum as a male reproductive toxicant. Environ Health Perspect 116(11):1473–1479

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Jacobs JJ, Skipor AK, Doorn PF, Campbell P, Schmalzried TP, Black J, Amstutz HC (1996) Cobalt and chromium concentrations in patients with metal on metal total hip replacements. Clin Orthop Relat Res 329(Suppl):S256–S263

    Article  PubMed  Google Scholar 

  24. Li H, Chen Q, Li S, Yao W, Li L, Shi X, Wang L, Castranova V, Vallyathan V, Ernst E, Chen C (2001) Effect of Cr(VI) exposure on sperm quality: human and animal studies. Ann Occup Hyg 45(7):505–511

    Article  CAS  PubMed  Google Scholar 

  25. Kumar S, Sathwara NG, Gautam AK, Agarwal K, Shah B, Kulkarni PK, Patel K, Patel A, Dave LM, Parikh DJ, Saiyed HN (2005) Semen quality of industrial workers occupationally exposed to chromium. J Occup Health 47(5):424–430

    Article  CAS  PubMed  Google Scholar 

  26. Geoffroy-Siraudin C, Perrard MH, Chaspoul F, Lanteaume A, Gallice P, Durand P, Guichaoua MR (2010) Validation of a rat seminiferous tubule culture model as a suitable system for studying toxicant impact on meiosis effect of hexavalent chromium. Toxicol Sci 116(1):286–296

    Article  CAS  PubMed  Google Scholar 

  27. Shi X, Ding M, Wang S, Leonard SS, Zang L, Castranova V, Vallyathan V, Chiu A, Dalal N, Liu K (1999) Cr(IV) causes activation of nuclear transcription factor NF-KB, DNA strand breaks and dG hydroxylation via free radical reactions. J Inorg Biochem 75(1):37–44

    Article  CAS  PubMed  Google Scholar 

  28. Pandey R, Singh SP (2002) Effects of molybdenum on fertility of male rats. Biometals 15(1):65–72

    Article  CAS  PubMed  Google Scholar 

  29. Lyubimov AV, Smith JA, Rousselle SD, Mercieca MD, Tomaszewski JE, Smith AC, Levine BS (2004) The effects of tetrathiomolybdate (TTM, NSC-714598) and copper supplementation on fertility and early embryonic development in rats. Reprod Toxicol 19(2):223–233

    Article  CAS  PubMed  Google Scholar 

  30. Kanaji A, Caicedo MS, Virdi AS, Sumner DR, Hallab NJ, Sena K (2009) Co-Cr-Mo alloy particles induce tumor necrosis factor alpha production in MLO-Y4 osteocytes: a role for osteocytes in particle-induced inflammation. Bone 45(3):528–533

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Tan SD, Kuijpers-Jagtman AM, Semeins CM, Bronckers AL, Maltha JC, Von den Hoff JW, Everts V, Klein-Nulend J (2006) Fluid shear stress inhibits TNFalpha-induced osteocyte apoptosis. J Dent Res 85(10):905–909

    Article  CAS  PubMed  Google Scholar 

  32. Ogata A, Yanagie H, Ishikawa E, Morishita Y, Mitsui S, Yamashita A, Hasumi K, Takamoto S, Yamase T, Eriguchi M (2008) Antitumour effect of polyoxomolybdates: induction of apoptotic cell death and autophagy in in vitro and in vivo models. Br J Cancer 98(2):399–409

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Golstein P, Kroemer G (2007) Cell death by necrosis: towards a molecular definition. Trends Biochem Sci 32(1):37–43

    Article  CAS  PubMed  Google Scholar 

  34. García-Rodríguez Mdel C, Carvente-Juárez MM, Altamirano-Lozano MA (2013) Antigenotoxic and apoptotic activity of green tea polyphenol extracts on hexavalent chromium-induced DNA damage in peripheral blood of CD-1 mice: analysis with differential acridine orange/ethidium bromide staining. Oxid Med Cell Longev 2013:486419

    PubMed  Google Scholar 

  35. Magaye R, Zhao J, Bowman L, Ding M (2012) Genotoxicity and carcinogenicity of cobalt-, nickel- and copper-based nanoparticles. Exp Ther Med 4(4):551–561

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Park E, Park K (2009) Oxidative stress and proinflammatory responses induced by silica nanoparticles in vivo and in vitro. Toxicol Lett 184(1):18–25

    Article  CAS  PubMed  Google Scholar 

  37. Alarifi S, Ali D, AO Y, Ahamed M, Siddiqui MA, Al-Khedhairy AA (2013) Oxidative stress contributes to cobalt oxide nanoparticles-induced cytotoxicity and DNA damage in human hepatocarcinoma cells. Int J Nanomedicine 8:189–199

    PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful for the assistance of Dr. Hatem SA El-Gohary, lecturer of Orthopedic, Mansoura Faculty of Medicine for his kind guidance during subject selection for the study.

Conflicts of interest

We declare that no benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. We also declare that we have no conflicts of interest in connection with this paper.

Author information

Authors and Affiliations

  1. Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, El-Gomhoria St., Mansoura, Egypt

    Ayman Z. Elsamanoudy & Dalia Shaalan

  2. Department of Dermatology, Andrology and STDs, Faculty of Medicine, Mansoura University, El-Gomhoria St., Mansoura, Egypt

    Mohammad A. Gaballah

  3. Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, El-Gomhoria St., Mansoura, Egypt

    Hend M. Abo El-Atta & Ahmed M.N. Helaly

Authors
  1. Ayman Z. Elsamanoudy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dalia Shaalan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mohammad A. Gaballah
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hend M. Abo El-Atta
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ahmed M.N. Helaly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dalia Shaalan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Elsamanoudy, A.Z., Shaalan, D., Gaballah, M.A. et al. Possible Effects of Metallosis on Spermatozoal Apoptotic Genes Expression in Individuals with Intramedullary Nailing Prosthesis. Biol Trace Elem Res 158, 334–341 (2014). https://doi.org/10.1007/s12011-014-9965-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-9965-z

Keywords

Search

Navigation