Abstract
Background
Human exposure to environmental pollutants is widespread. It was suggested that exposure to non-essential heavy metals may adversely affect semen development in men.
Purpose
To evaluate associations between non-essential heavy metals in blood and seminal fluid and semen quality parameters in men.
Methods
Male partners of heterosexual couples were included. The following elements were measured in blood and seminal fluid: lead (Pb), cadmium (Cd), arsenic (As), barium (Ba), mercury (Hg), and uranium (U) using ion-coupled plasma-mass spectrometry.
Setting
The fertility clinic at the American University of Beirut Medical Center.
Main outcome measures
Semen quality parameters (volume, concentration, total count, progressive motility, viability, and normal morphology).
Results
We found that participants with low-quality semen had significantly higher Cd and Ba concentrations in the seminal fluid than participants with normal-quality semen. We also observed significant associations between low sperm viability and higher blood Cd and Ba, as well as higher seminal Pb, Cd, Ba, and U. Furthermore, U concentrations in the seminal fluid were associated with increased odds ratios for below-reference progressive sperm motility and normal morphology.
Conclusions
Environmental exposures to Pb, Cd, Ba, and U appear to adversely influence sperm development in men. In non-occupationally exposed men, measurements of heavy metals in the seminal fluid may be more predictive of below-reference sperm quality parameters than in blood.
Similar content being viewed by others
References
Centers for Disease Control and Prevention. Second national report on human exposure to environmental chemicals. In Second national report on human exposure to environmental chemicals 2003. NCEH.
Centers for Disease Control and Prevention. Third national report on human exposure to environmental chemicals: executive summary. In Third national report on human exposure to environmental chemicals: executive summary 2005. NCEH.
ATSDR U. Toxicological profile for mercury (update) Atlanta, GA: US Agency for Toxic Substances and Disease Registry. 1999.
ATSDR U. Toxicological profile for arsenic. Agency for Toxic Substances and Disease Registry, Division of Toxicology, Atlanta, GA. 2007a.
ATSDR U. Toxicological profile for lead. US Department of Health and Human Services 2007b; 1:582.
ATSDR, Toxicological profile for cadmium 2012, in: Toxicological profiles. Agency for Toxic Substances and Disease Registry, 2012.
Hashisho Z, El-Fadel M. Socio-economic benefits of leaded gasoline phase-out: the case of Lebanon. J Environ Manag. 2001;12:389–406.
Salameh P, Bouchy N, Geahchan A. Hair lead concentration in the Lebanese population: phase 1 results. East Mediterr Health J. 2008;14
Carlsen E, Giwercman A, Keiding N, Skakkebæk NE. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992;305(6854):609–13.
Rolland M, Le Moal J, Wagner V, Royere D, De Mouzon J. Decline in semen concentration and morphology in a sample of 26,609 men close to general population between 1989 and 2005 in France. Hum Reprod. 2013;28:462–70.
Cooper TG, Noonan E, Von Eckardstein S, Auger J, Baker HG, Behre HM et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update 2009:dmp048.
Irvine S, Cawood E, Richardson D, MacDonald E, Aitken J. Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years. BMJ. 1996;312(7029):467–71.
Aneck-Hahn NH, Schulenburg GW, Bornman MS, Farias P, Jager C. Impaired semen quality associated with environmental DDT exposure in young men living in a malaria area in the Limpopo Province, South Africa. J Androl. 2007;28(3):423–34.
Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead and cadmium. Hum Reprod Update. 2000;6(2):107–21.
Benoff S, Hauser R, Marmar JL, Hurley IR, Napolitano B, Centola GM. Cadmium concentrations in blood and seminal plasma: correlations with sperm number and motility in three male populations (infertility patients, artificial insemination donors, and unselected volunteers). Mol Med. 2009;15(7–8):248–62.
Hernández-Ochoa I, García-Vargas G, López-Carrillo L, Rubio-Andrade M, Morán-Martínez J, Cebrián ME, et al. Low lead environmental exposure alters semen quality and sperm chromatin condensation in northern Mexico. Reprod Toxicol. 2005;20(2):221–8.
Moline JM, Golden AL, Bar-Chama N, Smith E, Rauch ME, Chapin RESM, et al. Exposure to hazardous substances and male reproductive health: a research framework. Environ Health Perspect. 2000;108(9):803–13.
Swan SH. Semen quality in fertile US men in relation to geographical area and pesticide exposure. Int J Androl. 2006;29(1):62–8.
Telisman S, Cvitković P, Jurasović J, Pizent A, Gavella M, Rocić B. Semen quality and reproductive endocrine function in relation to biomarkers of lead, cadmium, zinc, and copper in men. Environ Health Perspect. 2000;108(1):45–53.
Telišman S, Čolak B, Pizent A, Jurasović J, Cvitković P. Reproductive toxicity of low-level lead exposure in men. Environ Res. 2007;105(2):256–66.
Wong EW, Cheng CY. Impacts of environmental toxicants on male reproductive dysfunction. Trends Pharmacol Sci. 2011a;32:290–9.
Ebisch IM, Thomas CM, Peters WH, Braat DD, Steegers-Theunissen RP. The importance of folate, zinc and antioxidants in the pathogenesis and prevention of subfertility. Hum Reprod Update. 2007;13(2):163–74.
Thoreux-Manlay A, de la Calle JV, Olivier MF, Soufir JC, Masse R, Pinon-Lataillade G. Impairment of testicular endocrine function after lead intoxication in the adult rat. Toxicology. 1995;100:101–9.
Sarkar M, Chaudhuri GR, Chattopadhyay A, Biswas NM. Effect of sodium arsenite on spermatogenesis, plasma gonadotrophins and testosterone in rats. Asian J Androl. 2003;5(1):27–32.
ATSDR U. Toxicological profile for uranium US Department of Health and Human Services, Washington. 2011.
ATSDR. Toxicological profile for barium and barium compounds. US Department of Health and Human Services, Washington. 2007.
Sun J, Yu G, Zhang Y, Liu X, Du C, Wang L, et al. Heavy metal level in human semen with different fertility: a meta-analysis. Biol Trace Elem Res. 2016:1–10.
Mendiola J, Moreno JM, Roca M, Vergara-Juárez N, Martínez-García MJ, García-Sánchez A, et al. Relationships between heavy metal concentrations in three different body fluids and male reproductive parameters: a pilot study. Environ Health. 2011;10:6.
Oldereid NB, Thomassen Y, Attramadal A, Olaisen B, Purvis K. Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men. J Repro Fertil. 1993;99:421–5.
Sorensen MB, Stoltenberg M, Danscher G, Ernst E. Chelation of intracellular zinc ions affects human sperm cell motility. Mol Hum Reprod. 1999;5:338–41.
Inhorn MC, King L, Nriagu JO, Kobeissi L, Hammoud N, Awwad J, et al. Occupational and environmental exposures to heavy metals: risk factors for male infertility in Lebanon. Reprod Toxico. 2008;25:203–12.
World Health Organization. Examination and processing human semen 2010.
World Health Organization. Laboratory manual for the examination of human semen and semen cervical mucus interaction. Cambridge.1999.
Schisterman EF, Vexler A, Whitcomb BW, Liu A. The limitations due to exposure detection limits for regression models. Am J Epidemiol. 2006;163:374–83.
Amann RP. Considerations in evaluating human spermatogenesis on the basis of total sperm per ejaculate. J Androl. 2009;30(6):626–41.
Jensen TK, Gottschau M, Madsen JO, Andersson AM, Lassen TH, Skakkebæk NE, et al. Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men. BMJ Open. 2014;4(9):e005462.
Kim K, Bloom MS, Kruger PC, Parsons PJ, Arnason JG, Byun Y, et al. Toxic metals in seminal plasma and in vitro fertilization (IVF) outcomes. Environ Res. 2014;133:334–7.
Alexander BH, Checkoway H, Faustman EM, van Netten C, Muller CH, Ewers TG. Contrasting associations of blood and semen lead concentrations with semen quality among lead smelter workers. Am J Ind Med. 1998;34:464–9.
Robins TG, Bornman MS, Ehrlich RI, Cantrell AC, Pienaar E, Vallabh J, et al. Semen quality and fertility of men employed in a South African lead acid battery plant. Am J Ind Med. 1997;32:369–76.
Batra N, Nehru B, Bansal MP. Influence of lead and zinc on rat male reproduction at ‘biochemical and histopathological levels’. J Appl Toxicol. 2001;21(6):507–12.
Oliveira H, Spanò M, Santos C, de Lourdes Pereira M. Adverse effects of cadmium exposure on mouse sperm. Reprod Toxicol. 2009;28(4):550–5.
Pant N, Kumar G, Upadhyay AD, Gupta YK, Chaturvedi PK. Correlation between lead and cadmium concentration and semen quality. Andrologia. 2015;47(8):887–91.
Dawson EB, Ritter S, Harris WA, Evans DR, Powell LC. Comparison of sperm viability with seminal plasma metal levels. Biol Trace Elem Res. 1998;64:215–9.
Xu DX, Shen HM, Zhu QX, Chua L, Wang QN, Chia SE, et al. The associations among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. Mutat Res Genet Toxicol Environ Mutagen. 2003;534:155–63.
Meeker JD, Rossano MG, Protas B, Diamond MP, Puscheck E, Daly D, et al. Cadmium, lead, and other metals in relation to semen quality: human evidence for molybdenum as a male reproductive toxicant. Environ Health Perspect. 2008;116:1473–9.
Jurasović J, Cvitković P, Pizent A, Čolak B, Telišman S. Semen quality and reproductive endocrine function with regard to blood cadmium in Croatian male subjects. Biometals. 2004;17:735–43.
Keck C, Bramkamp G, Behre HM, Müller C, Jockenhövel F, Nieschlag E. Lack of correlation between cadmium in seminal plasma and fertility status of nonexposed individuals and two cadmium-exposed patients. ReprodToxicol. 1995;9(1):35–40.
Xu LC, Wang SY, Yang XF, Wang XR. Effects of cadmium on rat sperm motility evaluated with computer assisted sperm analysis. Biomed Environ Sci BES. 2001;14(4):312–7.
Hew KW, Ericson WA, Welsh MJ. A single low cadmium dose causes failure of spermiation in the rat. Toxicology and applied pharmacology. Toxicol Appl Pharmacol 1993;121(1):15–21.
El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH. Cadmium-induced changes in lipid peroxidation, blood hematology, biochemical parameters and semen quality of male rats: protective role of vitamin E and β-carotene. Food Chem Toxicol. 2004;42(10):1563–71.
Pant N, Pant AB, Chaturvedi PK, Shukla M, Mathur N, Gupta YK, et al. Semen quality of environmentally exposed human population: the toxicological consequence. Environ Sci Pollut Res Int. 2013;20(11):8274–81.
Kanwar U, Chadha S, Batla A, Sanyal SN, Sandhu R. Effect of selected metal ions on the motility and carbohydrate metabolism of ejaculated human spermatozoa. Physiol Pharmacol. 1988;32(3):195–201.
IARC, IARC monographs vol. 100C Evaluation of carcinogenic risks to humans, International Agency for Research on Cancer, Lyon, France. 2012.
Tarasenko NY, Pronin OA, Silayev AA. Barium compounds as industrial poisons (an experimental study). J Hyg Epidemol Microbiol Immunol. 1977;21(4):361–73.
Dietz DD, Elwell MR, Davis WE Jr, Meirhenry EF. Subchronic toxicity of barium chloride dihydrate administered to rats and mice in the drinking water. Fundam Appl Toxicol. 1992;19(4):527–37.
Squibb KS, McDiarmid MA. Depleted uranium exposure and health effects in Gulf War veterans. Philosophical transactions of the Royal Society of London Series B Biol Sci. 2006;361(1468):639–48.
Llobet JM, Sirvent JJ, Ortega A, Domingo J. Influence of chronic exposure to uranium on male reproduction in mice. Fundam Appl Toxicol. 1991;16(4):821–9.
Legendre A, Elie C, Ramambason C, Manens L, Souidi M, Froment P, et al. Endocrine effects of lifelong exposure to low-dose depleted uranium on testicular functions in adult rat. Toxicology. 2016;368:58–68.
Grignard E, Guéguen Y, Grison S, Lobaccaro JM, Gourmelon P, Souidi M. Contamination with depleted or enriched uranium differently affects steroidogenesis metabolism in rat. Int J Toxicol. 2008;27(4):323–8.
Arfsten DP, Schaeffer DJ, Johnson EW, Cunningham JR, Still KR, Wilfong ER. Evaluation of the effect of implanted depleted uranium on male reproductive success, sperm concentration, and sperm velocity. Environ Res. 2006;100(2):205–15.
Hao Y, Li R, Leng Y, Ren J, Liu J, Ai G, et al. A study assessing the genotoxicity in rats after chronic oral exposure to a low dose of depleted uranium. J Radiat Res. 2009;50(6):521–8.
Oliver IW, Graham MC, MacKenzie AB, Ellam RM, Farmer JG. Depleted uranium mobility across a weapons testing site: isotopic investigation of porewater, earthworms, and soils. Environ Sci Technol. 2008;42(24):9158–64.
De Angelis C, Galdiero M, Pivonello C, Salzano C, Gianfrilli D, Piscitelli P, et al. The environment and male reproduction: the effect of cadmium exposure on reproductive system and semen quality and its implication in fertility. Reprod Toxicol. 2017;73:105–27.
Liu J, Corton C, Dix DJ, Liu Y, Waalkes MP, Klaassen CD. Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice. Toxicol Appl Pharmacol. 2001;176(1):1–9.
Fujishiro H, Okugaki S, Yasumitsu S, Enomoto S, Himeno S. Involvement of DNA hypermethylation in down-regulation of the zinc transporter ZIP8 in cadmium-resistant metallothionein-null cells. Toxicol Appl Pharmacol. 2009;241(2):195–201.
Yang L, Li H, Yu T, Zhao H, Cherian MG, Cai L, et al. Polymorphisms in metallothionein-1 and-2 genes associated with the risk of type 2 diabetes mellitus and its complications. Am J Physiol Endocrinol Metab. 2008;294(5):E987–92.
Giacconi R, Bonfigli AR, Testa R, Sirolla C, Cipriano C, Marra M, et al. + 647 A/C and+ 1245 MT1A polymorphisms in the susceptibility of diabetes mellitus and cardiovascular complications. Mol Genet Metab. 2008;94(1):98–104.
Wirth JJ, Mijal RS. Adverse effects of low level heavy metal exposure on male reproductive function. Syst Biol Reprod Med. 2010;56(2):147–67.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
This study was approved by the American University of Beirut Institutional Review Board, and all eligible participants signed an informed consent form prior to enrollment.
Rights and permissions
About this article
Cite this article
Sukhn, C., Awwad, J., Ghantous, A. et al. Associations of semen quality with non-essential heavy metals in blood and seminal fluid: data from the Environment and Male Infertility (EMI) study in Lebanon. J Assist Reprod Genet 35, 1691–1701 (2018). https://doi.org/10.1007/s10815-018-1236-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10815-018-1236-z