Impact of heavy metals on the female reproductive system

Piotr Rzymski 1  ,  
Pawel Rzymski 2,  
Tomasz Opala 2,  
Department of Biology and Environmental Protection, Poznan University of Medical Sciences, Poznan, Poland
Department of Mother’s and Child’s Health, Poznan University of Medical Sciences, Poznan, Poland
Department of Educational Medicine, Poznan University of Medical Sciences, Poznan, Poland
Ann Agric Environ Med 2015;22(2):259–264
It has been recognized that environmental pollution can affect the quality of health of the human population. Heavy metals are among the group of highly emitted contaminants and their adverse effect of living organisms has been widely studied in recent decades. Lifestyle and quality of the ambient environment are among these factors which can mainly contribute to the heavy metals exposure in humans.

A review of literature linking heavy metals and the female reproductive system and description of the possible associations with emission and exposure of heavy metals and impairments of female reproductive system according to current knowledge.

The potential health disorders caused by chronic or acute heavy metals toxicity include immunodeficiency, osteoporosis, neurodegeneration and organ failures. Potential linkages of heavy metals concentration found in different human organs and blood with oestrogen-dependent diseases such as breast cancer, endometrial cancer, endometriosis and spontaneous abortions, as well as pre-term deliveries, stillbirths and hypotrophy, have also been reported.

Environmental deterioration can lead to the elevated risk of human exposure to heavy metals, and consequently, health implications including disturbances in reproduction. It is therefore important to continue the investigations on metal-induced mechanisms of fertility impairment on the genetic, epigenetic and biochemical level.

Piotr Rzymski   
Department of Biology and Environmental Protection, Poznan University of Medical Sciences, Poznan, Poland
1. Prüss-Üstün A, Corvalán C. Preventing disease through healthy environments. Towards an estimate of the environmental burden of disease. World Health Organization, France, 2006.
2. Järup L. Hazards of heavy metals contamination. British Medical Bulletin. 2003; 68(1): 167–182.
3. Rzymski P, Niedzielski P, Poniedziałek B, Klimaszyk P. Bioaccumulation of selected metals in bivalves (Unionidae) and Phragmites australis inhabiting a municipal water reservoir. Environmental Monitoring and Assessment 2014; 186: 3199–3212.
4. Duffus JH. “Heavy metal” – a meaningless term? Pure Appl Chem. 2002; 74(5): 793–807.
5. Szyczewski P, Siepak P, Niedzielski P, Sobczyński T. Research on heavy metals in Poland. Pol J Environ Stud. 2009; 18(5): 755–768.
6. Reeder RJ, Schoonen MAA, Lanzirotti A. Metal Speciation and Its Role in Bioaccessibility and Bioavailability. Rev Mineral and Geochem. 2006; 64: 59–113.
7. Edwards TM, Myers JP. Environmental Exposures and Gene Regulation in Disease Etiology. Environmental Health Perspectives 2007; 115(9): 1264–1270.
8. Pozharny Y, Lambertini L, Clunie G, Ferrara L, Lee MJ. Epigenetics in women’s health care. Mount Sinai Journal of Medicine 2010; 77(2): 225–235.
9. Arita A, Costa M. Epigenetics in metal carcinogenesis: Nickel, Arsenic, Chromium and cadmium. Metallomics 2009; 1: 222–228.
10. Salnikow K, Zhitkovich A. Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic and chromium. Chem. Res. Toxicol. 2008; 21(1): 28–44.
11. Larson J, Yasmin T, Sens D, Dong Zhou X, Sens M, Garret SH, et al. SPARC Gene Expression is Repressed in Human Urothelial Cells (UROtsa) Exposed to or Malignantly Transformed by Cadmium or Arsenite. Toxicology Letters 2010; 199(2): 166–172.
12. Florea A, Yamoah EN, Dopp E. Intracellular Calcium Disturbances Induced by Arsenic and Its Methylated Derivatives in Relation to Genomic Damage and Apoptosis Induction. Environmental Health Perspectives 2005; 113(6): 659–664.
13. Edwards TM, Myers JP. Environmental Exposures and Gene Regulation in Disease Etiology. Environmental Health Perspectives 2007; 115(9): 1264–1271.
14. Benbrahim-Tallaa L, Waterland R, Dill A, Webbe M, Waalkes M. Tumor Suppressor Gene Inactivation during Cadmium-Induced Malignant Transformation of Human Prostate Cells Correlates with Overexpression of de Novo DNA Methyltransferase. Environmental Health Perspectives 2007; 115(10): 1454–1459.
15. Zalejska- Fiolka J, Kasperczyk A, Birkner E, Kasperczyk S. Activity of superoxide dismutase and catalase in people protractedly exposed to lead compounds. Ann Agric Environ Med. 2004; 11(2): 291–296.
16. Jang DH, Hoffman RS. Heavy metal chelation in neurotoxic exposures. Neurologic Clinics 2011; 29(3): 607–622.
17. Youness ER, Mohammed NA, Morsy FA. Cadmium impact and osteoporosis: mechanism of action. Toxicology Mechanism and Methods 2012; 22(7): 560–567.
18. Hu H. Human health and heavy metals exposure. In: McCally M. (ed.). Life support: the environment and human health. MIT press, Massachusetts 2002; 4: 65–82.
19. Vayena E, Rowe PJ, Griffin PD. Medical, ethical & social aspects of assisted reproduction. Current practices & controversies in assisted reproduction: Report of a WHO meeting. Geneva, Switzerland 2001.
20. Quaas A, Dokras A. Diagnosis and Treatment of Unexplained Infertility. Reviews in Obstet Gynecol. 2008; 1(2): 69–76.
21. Sharpe RM, Franks S. Environment, lifestyle and infertility – an inter-generational issue. Nature Cell Biology 2002; 4(S1): 33–40.
22. Rzymski P, Rzymski P, Tomczyk K, Niedzielski P, Jakubowski K, Poniedziałek B, Opala T. Metal status in human endometrium: Relation to cigarette smoking and histological lesions. Environmental Research 2014; 132: 328–333.
23. Johnson M, Kenney N, Stoica A, Hilakivi-Clarke L, Singh B. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nature Medicine 2003; 9(8): 1081–1084.
24. Borja-Aburto V, Hertz-Picciotto I, Rojas Lopez M, Farias P, Camilo Rios, Blanco J. Blood lead levels measured prospectively and risk of spontaneous abortion. Am J Epidemiol. 1999; 150(6): 590–597.
25. Nasiadek M, Swiatkowska E, Nowinska A, Krawczyk T, Wilczynski J, Sapota A. The effect of cadmium on steroid hormones and their receptors in women with uterine myomas. Arch Environ Contamin Toxicol. 2011; 60(4): 734–741.
26. Akesson A, Julin B, Wolk A. Long- term dietary cadmium intake and postmenopausal endometrial cancer incidence: a population- based prospective cohort study. Cancer Research. 2008; 68(15): 6435–6441.
27. Jackson LW, Zullo MD, Goldberg JM. The association between heavy metals, endometriosis and uterine myomas among premenopausal women: National Health and Nutrition Examination Survey 1999–2002. Human Reproduction 2008; 23(3): 679–687.
28. Hofer N, Diel P, Wittsiepe J, Wilhelm M, Kluxen FM, Degen GH. Dose and route-dependent hormonal activity of the metalloestrogen cadmium in the rat uterus. Toxicology Letters. 2009; 191: 123–131.
29. Liu J, Huang H, Zhang W, Li H. Cadmium induced increase uterine wet weight and its mechanism. British Defects Research 2010; 89: 43–49.
30. Helmestam M, Stavreus-Evers A, Olovsson M. Cadmium chloride alters mRNA levels of angiogenesis related genes in primary human endometrial endothelial cells grown in vitro. Reproductive Toxicology 2010; 30: 370–376.
31. Oldereid N.B, Thomassen Y, Attramadal A, Olaisen B, Purvis K. Concentrations of lead, cadmium and zinc in the tissues of reproductive organs of men. J Rep Fertil. 1993; 99: 421–425.
32. Hertz-Picciotto I. The evidence that lead increases the risk for spontaneous abortion. Am J Ind Med. 2000; 38: 300–309.
33. Szkup-Jabłońska M, Karakiewicz B, Grochans E, Jurczak A, Nowak-Starz G, Rotter I et al. Effects of blood lead and cadmium levels on the functioning of children with behaviour disorders in the family environment. Ann Agric Environ Med. 2012; 19(2): 241–246.
34. Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ. The effect of occupational exposure to mercury vapor on the fertility of female dental assistants. Occup Environ Med. 1994; 51(1): 28–34.
35. Schuurs AH. Reproductive toxicity of occupational mercury. A review of the literature. Journal of Dentistry 1999; 27(4): 249–256.
36. Davis BJ, Price HC, O’Connor RW, Fernando R, Rowland AS, Morgan DL. Mercury vapor and female reproductive toxicity. Toxicology Science 2001; 59(2): 291–296.
37. Lee BE, Hong YC, Park H, Ha M, Koo BS, Chang N, et al. Interaction between GSTM1/GSTT1 polymorphism and blood mercury on birth weight. Environmental Health Perspectives. 2010; 118(3): 437–443.
38. Karagas MR, Choi AL, Oken E, Horvat M, Schoeny R, Kamai E. Evidence of the human health effects of low-level methylmercury exposure. Environmental Health Perspectives. 2012; 120(6): 799–806.
39. McGrath SP, Chaudri AM, Giller KE. Long-term effects of metals in sewage sludge on soils, microorganism and plants. J Ind Microbiol Biotechnol. 1995; 14(2): 94–104.
40. Bednarski B, Goryński P, Łata E, Parchimowicz T, Przewoźniak K. Ministry of Health Report for WHO. Poland. 2007/2008: 23–73.
41. Fronczak A, Polańska K, Makowiec-Dabrowska T, Kaleta D. Smoking among women-strategies for fighting the tobacco epidemic. Przeg Lek. 2012; 69(10): 929–933.
42. Ashraf MW. Levels of heavy metals in popular cigarette brands and exposure to these metals via smoking. Sci World J. 2012; 2012: 729430.
43. Jensen TK, Henriksen TB, Hjollund NH, Scheike T, Kolstad H, et al. Adult and prenatal exposures to tobacco smoke as risk indicators of fertility among 430 Danish couples. Am J Epid. 1998; 148(10): 992–997.
44. Wdowiak A, Lewicka M, Plewka K, Bakalczuk G. Nikotinism and quality of embryos obtained in in-vitro fertilization programmes. Ann Agric Environ Med. 2013; 20(1): 82–85.
45. Dechanet C, Brunet C, Anahory T, Hamamah S, Hedon B, Dechaud H. Effect of cigarette smoking of embryo implantation and placentation and analysis of factors interfering with cigarette smoke effects (part II). Gynecologie Obstetrique and Fertilite 2011; 39(10): 567–574.
46. Been J, Nurmatov U, van Schayck C, Sheikh A. The impact of smoke – free legislation on fetal, infant and child health: a systematic review and meta- analysis protocol. BMJ Open. 2013; 3(2): 1–4.
47. Clifford A, Lang L, Chen R. Effects of maternal cigarette smoking during pregnancy on cognitive parameters of children and young adults: a literature review. Neurotoxicology and Teratology. 2012; 34(6): 560–570.
48. Klejewski A, Urbaniak T, Pisarska-Krawczyk M, Sobczyk K. Influence of smoking on pregnancy. Przegl Lek. 2012; 69(10): 929–933.
49. Jabłonowska D, Marszałek A, Bodnar M. Tobacco smoking, HPV infection and changes in cervix. Przegl Lek. 2012; 69(10): 740–743.
50. Cerqueira EM, Santoro CL, Donozo NF, Freitas BA, Pereira CA, et al. Genetic demage in exfoliated cells of the uterine cervix. Association and interaction between cigarette smoking and progression to malignant transformation? Acta Cytologica 1998; 42(3): 639–49.
51. Zhou Y, Jorgensen E,Gan Y, Taylor H. Cigarette smoke increases progesterone receptor and homeobox A10 expression in human endometrium and endometrial cells: a potential role in the decreased prevalence of endometrial pathology in smokers. Biology of reproduction. 2011; 84: 1242–1247.
52. Davar R, Sekhavat L, Naserzadeh N. Semen parameters of non-infertile smoker and non-smoker men. Journal of Medicine and Life. 2012; 5(4): 465–468.
53. Mitra A, Chakraborty B, Mukhopadhay D, Pal M, Mukherjee S, et al. Effect of smoking on semen quality, FSH, testosterone level, and CAG repeat length in androgen receptor gene of infertile men in an Indian city. Syst Biol Reprod Med. 2012, 58:255–62.
54. Taszarek H, Depa-Martynów M, Derwich K, Pawelczyk L, Jędrzejczak P. The influence of cigarette smoking on sperm quality of male smokers and nonsmokers in infertile couples. Przegl Lek. 2005; 62(10): 978–981.
55. Hassa H, Yildrim A. Effect of smoking on semen parameters of men attending an infertility clinic. Clin Exp Obstet Gynecol. 2006; 33(1): 19–22.