Biological Trace Element Research

, Volume 175, Issue 2, pp 244–253 | Cite as

Mapping Fifteen Trace Elements in Human Seminal Plasma and Sperm DNA

  • Sazan Ali
  • Florence Chaspoul
  • Loundou Anderson
  • David Bergé-Lefranc
  • Vincent Achard
  • Jeanne Perrin
  • Philippe Gallice
  • Marie Guichaoua


Studies suggest a relationship between semen quality and the concentration of trace elements in serum or seminal plasma. However, trace elements may be linked to DNA and capable of altering the gene expression patterns. Thus, trace element interactions with DNA may contribute to the mechanisms for a trans-generational reproductive effect. We developed an analytical method to determine the amount of trace elements bound to the sperm DNA, and to estimate their affinity for the sperm DNA by the ratio: R = Log [metal concentration in the sperm DNA/metal concentration in seminal plasma]. We then analyzed the concentrations of 15 trace elements (Al, Cd, Cr, Cu, Hg, Mn, Mo, Ni, Pb, Ti, V, Zn, As, Sb, and Se) in the seminal plasma and the sperm DNA in 64 normal and 30 abnormal semen specimens with Inductively Coupled Plasma/Mass Spectrometry (ICP-MS). This study showed all trace elements were detected in the seminal plasma and only metals were detected in the sperm DNA. There was no correlation between the metals’ concentrations in the seminal plasma and the sperm DNA. Al had the highest affinity for DNA followed by Pb and Cd. This strong affinity is consistent with the known mutagenic effects of these metals. The lowest affinity was observed for Zn and Ti. We observed a significant increase of Al linked to the sperm DNA of patients with oligozoospermia and teratozoospermia. Al’s reproductive toxicity might be due to Al linked to DNA, by altering spermatogenesis and expression patterns of genes involved in the function of reproduction.


Trace elements Reproductive toxicant Sperm DNA Seminal plasma DNA adducts Mutations 



We thank C. Metton, M.J. Fays-Bernardin, and D. Daioglou for their technical assistance as well as Germetheque for their support.

Compliance with Ethical Standards

Funding Source and Approval Committee

GERMETHEQUE biobank (France, Marseille University Hospital la Conception) provided all samples and exposure data. In accordance with the 1975 Helsinki Declaration on human experimentation, GERMETHEQUE obtained consent to use each participant’s samples in the human fertility studies. The Germetheque scientific committee approved the study design, and, as a consequence, GERMETHEQUE was validated by the Institutional Review Board (CPP Sud-Ouest and Outremer, n°2-15-27).

The Germetheque sample collection was supported by grants from the ANR (Agence Nationale pour la Recherche), the ABM (Agence de la Biomédecine), the Centre Hospitalier Universitaire de Toulouse, and APHM (Assistance Publique Hôpitaux de Marseille).


  1. 1.
    Geoffroy-Siraudin C, Loundou AD, Romain F, Achard V, Courbiere B, Perrard MH, et al. (2012) Decline of semen quality among 10 932 males consulting for couple infertility over a 20-year period in Marseille, France. Asian J Androl 14:584–590CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Al Bakheet SA, Attafi IM, Maayah ZH, Abd-Allah AR, Asiri YA, Korashy HM (2013) Effect of long-term human exposure to environmental heavy metals on the expression of detoxification and DNA repair genes. Environ Pollut 181:226–232CrossRefPubMedGoogle Scholar
  3. 3.
    Godschalk R, Hogervorst J, Albering H, Mercelina-Roumans P, van Schooten FJ, de Haan J, et al. (2005) Interaction between cadmium and aromatic DNA adducts in hprt mutagenesis during foetal development. Mutagenesis 20:181–185CrossRefPubMedGoogle Scholar
  4. 4.
    Xu DX, Shen HM, Zhu QX, Chua L, Wang QN, Chia SE, et al. (2003) The associations among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. Mutat Res 534:155–163CrossRefPubMedGoogle Scholar
  5. 5.
    Venkatramreddy V, Tchounwou PB (2013) Oxidative stress and DNA damage induced by chromium in liver and kidney of goldfish, Carassius auratus. Biomark Insights 8:43–51Google Scholar
  6. 6.
    Caicedo M, Jacobs JJ, Reddy A, Hallab NJ (2007) Analysis of metal ion-induced DNA damage, apoptosis, and necrosis in human (Jukart) T-cells demonstrates Ni2+ and V3+ are more toxic than other metals: Al3+, Be2+, Co2+, Cr3+, Cu2+, Fe3+, Mo5+, Nb5+, Zr2+. J Biomed Mater Res Part A:905–913Google Scholar
  7. 7.
    Kawata K, Shimazaki R, Okabe S (2009) Comparison of gene expression profiles in HepG2 cells exposed to arsenic, cadmium, nickel, and three model carcinogens for investigating the mechanisms of metal carcinogenesis. Environ Mol Mutagen 50:46–59CrossRefPubMedGoogle Scholar
  8. 8.
    Sorokin VA, Valeev VA, Gladchenko GO, Sysa IV, Blagoi YP, Volchok IV (1996) Interaction of bivalent copper, nickel, manganese ions with native DNA and its monomers. J Inorg Biochem 63:79–98CrossRefPubMedGoogle Scholar
  9. 9.
    Mazzuca D, Russo N, Toscano M, Grand A (2006) On the interaction of bare and hydrated aluminum ion with nucleic acid bases (U, T, C, a, G) and monophosphate nucleotides (UMP, dTMP, dCMP, dAMP, dGMP). J Phys Chem B 110:8815–8824CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang X, Wang F, Liu B, Kelly EY, Servos MR, Liu J (2014) Adsorption of DNA oligonucleotides by titanium dioxide nanoparticles. Langmuir 30:839–845CrossRefPubMedGoogle Scholar
  11. 11.
    Millonig H, Pous J, Gouyette C, Subirana JA, Campos JL (2009) The interaction of manganese ions with DNA. J Inorg Biochem 103:876–880CrossRefPubMedGoogle Scholar
  12. 12.
    Smith NM, Amrane S, Rosu F, Gabelica V, Mergny JL (2012) Mercury-thymine interaction with a chair type G-quadruplex architecture. Chem Commun (Cambridge, England) 48:11464–11466CrossRefGoogle Scholar
  13. 13.
    Koc H, Swenberg JA (2002) Applications of mass spectrometry for quantification of DNA adducts. J Chromatogr 778:323–343Google Scholar
  14. 14.
    Carette D, Perrard MH, Prisant N, Gilleron J , Pointis G, Segretain D, Durand D. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin-43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model. Toxicol Appl Pharmacol 2013;268:27–36.CrossRefPubMedGoogle Scholar
  15. 15.
    Chung NP, Cheng CY (2001) Is cadmium chloride-induced inter-Sertoli tight junction permeability barrier disruption a suitable in vitro model to study the events of junction disassembly during spermatogenesis in the rat testis? Endocrinology 142:1878–1888PubMedGoogle Scholar
  16. 16.
    Oldereid NB, Thomassen Y, Purvis K (1998) Selenium in human male reproductive organs. Hum Reprod 13:2172–2176CrossRefPubMedGoogle Scholar
  17. 17.
    Bjorndahl L, Kvist U (2010) Human sperm chromatin stabilization: a proposed model including zinc bridges. Mol Hum Reprod 16:23–29CrossRefPubMedGoogle Scholar
  18. 18.
    Lai JC, Lai MB, Jandhyam S, Dukhande VV, Bhushan A, Daniels CK, et al. (2008) Exposure to titanium dioxide and other metallic oxide nanoparticles induces cytotoxicity on human neural cells and fibroblasts. Int J Nanomedicine 3:533–545PubMedPubMedCentralGoogle Scholar
  19. 19.
    Ema M, Kobayashi N, Naya M, Hanai S, Nakanishi J (2010) Reproductive and developmental toxicity studies of manufactured nanomaterials. Reprod Toxicol (Elmsford, NY) 30:343–352CrossRefGoogle Scholar
  20. 20.
    Peto MV (2010) Aluminium and iron in humans: bioaccumulation, pathology, and removal. Rejuvenation Res 13:589–598CrossRefPubMedGoogle Scholar
  21. 21.
    Kim H, Lee HJ, Hwang JY, Ha EH, Park H, Ha M, et al. (2010) Blood cadmium concentrations of male cigarette smokers are inversely associated with fruit consumption. J Nutr 140:1133–1138CrossRefPubMedGoogle Scholar
  22. 22.
    Barceloux DG (1999) Chromium. J Toxicol Clin Toxicol 37:173–194CrossRefPubMedGoogle Scholar
  23. 23.
    Von Burg R, Liu D (1993) Chromium and hexavalent chromium. J Appl Toxicol 13:225–230CrossRefGoogle Scholar
  24. 24.
    World Health Organisation (2010) WHO Laboratory manual for the examination and processing of human semen. WHO Press, GenevaGoogle Scholar
  25. 25.
    Auger J, Eustache F, David G (2000) Standardisation de la classification morphologique des spermatozoïdes humains selon la méthode de David modifiée. Andrologie 10:358–373CrossRefGoogle Scholar
  26. 26.
    Queiroz EK, Waissmann W (2006) Occupational exposure and effects on the male reproductive system. Cad Saude Publica 22:485–493CrossRefPubMedGoogle Scholar
  27. 27.
    Minguez-Alarcon L, Mendiola J, Roca M, Lopez-Espin JJ, Guillen JJ, Moreno JM, et al. (2012) Correlations between different heavy metals in diverse body fluids: studies of human semen quality. Adv Urol 2012:420893CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Giaccio L, Cicchella D, De Vivo B, Lombardi G, De Rosa M (2012) Does heavy metals pollution affects semen quality in men? A case of study in the metropolitan area of Naples (Italy). J Geochem Explor 112:218–225CrossRefGoogle Scholar
  29. 29.
    Benoff S, Centola GM, Millan C, Napolitano B, Marmar JL, Hurley IR (2003) Increased seminal plasma lead levels adversely affect the fertility potential of sperm in IVF. Hum Reprod 18:374–383CrossRefPubMedGoogle Scholar
  30. 30.
    Mendiola J, Moreno JM, Roca M, Vergara-Juarez N, Martinez-Garcia MJ, Garcia-Sanchez A, et al. (2011) Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study. Environ Health 10:6CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Telisman S, Cvitkovic P, Jurasovic J, Pizent A, Gavella M, Rocic B (2000) Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ Health Perspect 108:45–53CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Telisman S, Colak B, Pizent A, Jurasovic J, Cvitkovic P (2007) Reproductive toxicity of low-level lead exposure in men. Environ Res 105:256–266CrossRefPubMedGoogle Scholar
  33. 33.
    Li P, Zhong Y, Jiang X, Wang C, Zuo Z, Sha A (2012) Seminal plasma metals concentration with respect to semen quality. Biol Trace Elem Res 148:1–6CrossRefPubMedGoogle Scholar
  34. 34.
    Rossman TG, Klein CB (2011) Genetic and epigenetic effects of environmental arsenicals. Metallomics 3:1135–1141CrossRefPubMedGoogle Scholar
  35. 35.
    ViIlaverde AISB, Fioratti EG, Ramos RS, Neves RCF, Ferreira JCP, Cardoso GS, Padilha PM, Lopes MD (2014) Blood and seminal plasma concentrations of selenium, zinc and testosterone and their relationship to sperm quality and testicular biometry in domestic cats. Anim Reprod Sci 150:50–55CrossRefGoogle Scholar
  36. 36.
    Atig F, Raffa M, Habib BA, Kerkeni A, Saad A, Ajina M (2012) Impact of seminal trace element and glutathione levels on semen quality of Tunisian infertile men. BMC Urol 12:6–13CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Figa-Talamenca I, Traina ME, Urbani E (2001) Occupational exposure to metals, solvents and pesticides: recent evidence on male reproductive effects and biological markers. Occup Med 51:174–188CrossRefGoogle Scholar
  38. 38.
    Hovatta O, Venalainen ER, Kuusimaki L, Heikkila J, Hirvi T, Reima I (1998) Aluminium, lead and cadmium concentrations in seminal plasma and spermatozoa, and semen quality in Finnish men. Hum Reprod 13:115–119CrossRefPubMedGoogle Scholar
  39. 39.
    Klein JP, Mold M, Mery L, Cottier M, Exley C (2014) Aluminum content of human semen: implications for semen quality. Reprod Toxicol (Elmsford, NY) 50:43–48CrossRefGoogle Scholar
  40. 40.
    Alexander BH, Checkoway H, Faustman EM, van Netten C, Muller CH, Ewers TG (1998) Contrasting associations of blood and semen lead concentrations with semen quality among lead smelter workers. Am J Ind Med 34:464–469CrossRefPubMedGoogle Scholar
  41. 41.
    Exley C (2013) Human exposure to aluminium. Environ Sci Process Impacts 15:1807–1816CrossRefPubMedGoogle Scholar
  42. 42.
    Bagchi D, Stohs SJ, Downs BW, Bagchi M, Preuss HG (2002) Cytotoxicity and oxidative mechanisms of different forms of chromium. Toxicology 180:5–22CrossRefPubMedGoogle Scholar
  43. 43.
    Aduayom I, Campbell PG, Denizeau F, Jumarie C (2003) Different transport mechanisms for cadmium and mercury in Caco-2 cells: inhibition of Cd uptake by Hg without evidence for reciprocal effects. Toxicol Appl Pharmacol 189:56–67CrossRefPubMedGoogle Scholar
  44. 44.
    Zhang RY, Liu Y, Pang DW, Cai RX, Qi YP (2002) Spectroscopic and voltammetric study on the binding of aluminium (III) to DNA. Anal Sci 18:761–766CrossRefPubMedGoogle Scholar
  45. 45.
    Rani A, Kumar A, Lal A, Pant M (2014) Cellular mechanisms of cadmium-induced toxicity: a review. Int J Environ Health Res 24:378–399CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Sazan Ali
    • 1
    • 2
  • Florence Chaspoul
    • 2
    • 3
  • Loundou Anderson
    • 4
  • David Bergé-Lefranc
    • 2
    • 3
  • Vincent Achard
    • 2
    • 5
  • Jeanne Perrin
    • 2
    • 5
  • Philippe Gallice
    • 2
    • 3
  • Marie Guichaoua
    • 2
  1. 1.Department of Biology, Faculty of Science and Education Sciences, School of ScienceUniversity of SulaimaniSulaimaniIraq
  2. 2.IMBE, UMR CNRS, IRD, Faculté de MédecineAix Marseille Université, Avignon UniversitéMarseilleFrance
  3. 3.Laboratoire de Chimie Physique et Prévention des risques et Nuisances Technologiques, Faculté de PharmacieMarseilleFrance
  4. 4.Methodological Assistance Unity for Clinical Research, Department of Public Health, Faculty of MedicineMarseilleFrance
  5. 5.Department of Gynecology Obstetrics and Reproduction (Gynepole)CECOS Laboratory of Biology of Reproduction, AP-HM La Conception University HospitalMarseilleFrance

Personalised recommendations