Skip to main content

Advertisement

Log in

Perspectives in Endocrine Toxicity of Heavy Metals—A Review

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

Abstract

An attempt has been made to review the endocrine/hormonal implications of a few environmentally significant metals, viz, lead, mercury, cadmium, copper, arsenic and nickel, in man and animals. Special emphasis has been given to the adrenals, thyroid, testis, ovary and pancreas. Toxic metals can cause structural and functional changes in the adrenal glands. Their effects on steroidogenesis have been reviewed. It has been reported that thyroid hormone kinetics are affected by a number of metallic compounds. Occupational exposure to a few of these metals can cause testicular injury and sex hormone disturbances. Protective effects of a few antioxidants on their reproductive toxicity have also been discussed. Information gathered on female reproductive toxicity of heavy metals shows that exposure to these metals can lead to disturbances in reproductive performance in exposed subjects. Certain metals can cause injury to the endocrine pancreas. Exposure to them can cause diabetes mellitus and disturb insulin homeostasis. The need to develop molecular markers of endocrine toxicity of heavy metals has been suggested. Overall information described in this review is expected to be helpful in planning future studies on endocrine toxicity of heavy metals.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

c-AMP:

Cyclic adenosine monophosphate

ACTH:

Adrenocorticotrophic hormone

GH:

Growth hormone

TSH:

Thyroid-stimulating hormone

PbB:

Lead in blood

RAR:

Retinoic acid receptor

CNS:

Central nervous system

UDP:

Uridine phosphate

EPA:

Environmental Protection Agency

ROS:

Reactive oxygen species

ATSDR:

Agency for Toxic Substances and Disease Registry

PGF:

Prostaglandin F

FSH:

Follicle-stimulating hormone

LH:

Luteinizing hormone

MT:

Metallothionein

HIT-T15:

Hamster insulinoma tumour β cells

RIN-m5F:

Radiation-induced β cells

References

  1. Harvey PW (1996) An overview of adrenal gland involvement in toxicology: from target organ to stress and glucocorticoid modulation of toxicity. In: Harvey PW (ed) The adrenal in toxicology: target organ and modulator of toxicity. Taylor and Francis, London

    Google Scholar 

  2. Friberg L, Nordberg GF, Vouk V (1986) Handbook on the toxicology of metals, 2nd ed. Volume 1: general aspects. Elsevier, Amsterdam, New York, Oxford

  3. Goyer RA, Klaassen CD, Waalkes MP (1995) Metal toxicology. Academic, San Diego, New York, London, Sydney, Tokyo, Toronto

    Google Scholar 

  4. Hughes MN (1972) The inorganic chemistry of biological processes. Wiley, New York

    Google Scholar 

  5. Hart DT, Borowitz JL (1974) Adrenal catecholamine release by divalent mercury and cadmium. Arch Int Pharmacodyn Ther 209:94–99

    CAS  PubMed  Google Scholar 

  6. Burton GV, Meikle AW (1980) Acute and chronic methyl mercury poisoning in impairs rat adrenal and testicular function. J Toxicol Environ Health 6:597–606

    CAS  PubMed  Google Scholar 

  7. Fernicola C, Govoni S, Coniglio L, Trabucchi M (1985) Toxicologic hazards at the endocrine level of the heavy metals. G Ital Med Lav 7:175–180

    CAS  PubMed  Google Scholar 

  8. Ng TB, Liu WK (1990) Toxic effects of heavy metals on cells isolated from rat adrenal and testis. In Vitro Cell Dev Biol 26:24–28

    CAS  PubMed  Google Scholar 

  9. Barregard L, Lindstedt G, Schutz A, Sallsten G (1994) Endocrine function in mercury exposed chloralkali workers. Occup Environ Med 51:536–540

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Leblond VS, Hontela A (1999) Effects of in vitro exposure to cadmium, mercury, zinc and 1-(2-chlorophenyl)-1-(4-chlorphenyl)-2,2-dichkloroethane on steroidogenesis by dispersed interregnal cells of rainbow trout (Oncorhynchus mykiss). Toxicol Appl Pharmacol 157:16–22

    CAS  PubMed  Google Scholar 

  11. Ranyal NJ, Hontela A, Jumarie C (2005) Cadmium uptake in isolated adrenocortical cells of rainbow trout and yellow perch. Comp Biochem Physiol C 140:374–382

    Google Scholar 

  12. Wada H, Cristol DA, McNabb FM, Hopkins WA (2009) Suppressed adrenocortical responses and thyroid hormone levels in birds near a mercury contaminated river. Environ Sci Technol 43:6031–6038

    CAS  PubMed  Google Scholar 

  13. Lafuente A, Esquifino A (1999) Cadmium effects on hypothalamic activity and pituitary hormone secretion in the male. Toxicol Lett 110:209–218

    CAS  PubMed  Google Scholar 

  14. Lafuente A, Cano P, Esquifino A (2003) Are cadmium effects on plasma gonadotropins, prolactin, ACTH, GH and TSH levels, dose dependent? Biometals 16:243–250

    CAS  PubMed  Google Scholar 

  15. Nishiyama S, Nakamura K, Ogawa M (1985) Effects of heavy metals on corticosteroid production in cultured rat adrenocortical cells. Toxicol Appl Pharmacol 81:174–176

    CAS  PubMed  Google Scholar 

  16. Sandhu N, Vijayan MM (2011) Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout. Aquat Toxicol 103:92–100

    CAS  PubMed  Google Scholar 

  17. Caride A, Fernandez-Perez B, Cabaleiro T, Tarasco M, Esquifino A, Lafuente A (2010) Cadmium chronotoxicity at pituitary level: effects on plasma ACTH, GH, and TSH daily pattern. J Physiol Biochem 66:213–220

    CAS  PubMed  Google Scholar 

  18. Shrivastava VK, Sathyanesan AG (1988) Effect of cadmium chloride on thyroid activity of the female Indian palm squirrel, Funambulus pennanti (Wroughton). Bull Environ Contam Toxicol 40:268–272

    CAS  PubMed  Google Scholar 

  19. Yoshizuka M, Mori N, Hamasaki K, Tanaka I, Yokoyama M, Hara K, Doi Y, Umezu Y, Araki H, Sakamoto Y et al (1991) Cadmium toxicity in the thyroid gland of pregnant rats. Exp Mol Pathol 55:97–104

    CAS  PubMed  Google Scholar 

  20. Pavia Hunior MA, Paier B, Noli MI, Hagmuller K, Zaninovich AA (1997) Evidence suggesting that cadmium induces a non-thyroidal illness syndrome in the rat. J Endocrinol 154:113–117

    Google Scholar 

  21. Pilat-Marcinkiewicz B, Sawicki B, Brzoska MM, Moniuszko-Jakoniuk J (2002) Effect of chronic administration of cadmium on the rat thyroid: radioimmunological and immunohistochemical studies. Folia Histochem Cytobiol 40:189–190

    CAS  PubMed  Google Scholar 

  22. Singh B, Chandran V, Bandhu HK, Mittal BR, Bhattacharya A, Jindal SK, Verma S (2000) Impact of lead exposure on pituitary-thyroid axis in humans. Biometals 13:187–192

    CAS  PubMed  Google Scholar 

  23. Liang QR, Liao RQ, Su SH, Huang SH, Pan RH, Huang JL (2003) Effects of lead on thyroid function of occupationally exposed workers. Zhonghua Lao Dong Wei Sheng Zhi Ye Bing ZA Zhi 21:111–113

    PubMed  Google Scholar 

  24. Doumouchtsis KK, Doumouschtsis SK, Doumouchtsis EK, Perrea DN (2009) The effect of lead intoxication on endocrine functions. Endocrinol Investig 32:175–183

    CAS  Google Scholar 

  25. Ibrahim NM, Eweis EA, El-Beltagi HS, Abdel-Mobdy YE (2012) Effect of lead acetate toxicity on experimental male albino rats. Asian Pac J Trop Biomed 2:41–46

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Mahmood T, Qureshi IZ, Iqbal MJ (2010) Histopathological and biochemical changes in rat thyroid following acute exposure to hexavalent chromium. Histol Histopathol 25:1355–1370

    PubMed  Google Scholar 

  27. Qureshi IZ, Mahmood T (2010) Prospective role of ascorbic acid (vitamin C) in attenuating hexavalent chromium induced functional and cellular damage in rat thyroid. Toxicol Ind Health 26:349–359

    CAS  PubMed  Google Scholar 

  28. Allen T, Rana SVS (2007) Effect of n-propylthiouracil or thyroxine on arsenic trioxide toxicity in the liver of rat. J Trace Elem Med Biol 21:194–203

    CAS  PubMed  Google Scholar 

  29. Liu F, Gentles A, Theodorakis CW (2008) Arsenate and perchlorate toxicity, growth effects, and thyroid histopathology in hypothyroid zebra fish, Danio rerio. Chemosphere 71:1369–1376

    CAS  PubMed  Google Scholar 

  30. Davey JC, Nomikos AP, Wungjiranirun M, Sherman JR, Ingram L, Batki C, Lariviere JP, Hamilton JW (2008) Arsenic as an endocrine disruptor: arsenic disrupts retinoic acid receptor-and thyroid hormone receptor-mediated gene regulation and thyroid hormone-mediated amphibian tail metasmorphosis. Environ Health Perspect 116:165–172

    CAS  PubMed Central  PubMed  Google Scholar 

  31. Zhang L, Wang J, Zhu GN, Su L (2010) Pubertal exposure to thiodiazole copper inhibits thyroid function in juvenile female rats. Exp Toxicol Pathol 62:163–169

    CAS  PubMed  Google Scholar 

  32. Iijima K, Otake T, Yoshinaga J, Ikegami M, Suzuki E, Naruse H, Yamanaka T, Shinuya N, Yasumizu T, Kato N (2007) Cadmium, lead and selenium in cord blood and thyroid hormone status of newborns. Biol Trace Elem Res 119:10–18

    CAS  PubMed  Google Scholar 

  33. Leblondel G, Le Bouil A, Allain P (1992) Influence of thyroparathyroidectomy and thyroxine replacement on Cu and Zn cellular distribution and on metallothionein level and induction in rats. Biol Trace Elem Res 32:281–288

    CAS  PubMed  Google Scholar 

  34. Mehta J, Dhawan D, Mehta M, Kumar R, Chopra JS, Sharma RR (1986) Effect of dietary cadmium intake on serum thyroxine and triiodothyronine concentrations in rhesus monkeys. Toxicol Lett 34:85–88

    CAS  PubMed  Google Scholar 

  35. Sin YM, Teh WF (1992) Effect of long term uptake of mercuric sulphide on thyroid hormones and glutathione in mice. Bull Environ Contam Toxicol 49:847–854

    CAS  PubMed  Google Scholar 

  36. Mendy A, Gasana J, Vieira ER (2013) Low blood lead concentrations and thyroid function of American adults. Int J Environ Health Res 23(6):461–473

    CAS  PubMed  Google Scholar 

  37. Danielsson BR, Dencker L, Lindgren A, Tjalve H (1984) Accumulation of toxic metals in male reproductive organs. Arch Toxicol Suppl 7:177–180

    CAS  PubMed  Google Scholar 

  38. Friberg L, Piscator M, Nordberg GF (1974) Cadmium in the environment, 2nd edn. CRC Press, Cleveland, pp 37–53

    Google Scholar 

  39. Goyer RA, Liu J, Waalkes MP (2004) Cadmium and cancer of prostate and testis. Biometals 17:555–558

    CAS  PubMed  Google Scholar 

  40. Martynowicz H, Skoczynska A, Karczmarek-Wdowiak B, Andrzejak R (2005) Effects of cadmium on testis function. Med Pr 56:167–174

    CAS  PubMed  Google Scholar 

  41. Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559

    CAS  PubMed  Google Scholar 

  42. Gunnarsson D, Nordberg G, Selstam G (2007) Differential effects of cadmium on the gene expression of seven-transmembrane-spanning receptors and GAPDH in the rat testis. Toxicol Lett 168:51–57

    CAS  PubMed  Google Scholar 

  43. Takiguchi M, Yoshihara S (2006) New aspects of cadmium as endocrine disruptor. Environ Sci 13:107–116

    CAS  PubMed  Google Scholar 

  44. Siu ER, Mruk DD, Porto CS, Cheng CY (2009) Cadmium-induced testicular injury. Toxicol Appl Pharmacol 238:240–249

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Thompson J, Bannigan J (2008) Cadmium: toxic effects on the reproductive system and the embryo. Reprod Toxicol 25:304–315

    CAS  PubMed  Google Scholar 

  46. Burukoglu D, Baycu C (2008) Protective effects of zinc on testis of cadmium treated rats. Bull Environ Contam Toxicol 81:521–524

    CAS  PubMed  Google Scholar 

  47. Liu J, Qu W, Kadiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 1238:209–214

    Google Scholar 

  48. Nava-Hernandez MP, Hauad-Marroquin LA, Bassol-Mayagoitia S, Garcia-Arenas G, Mercado-Hernandez R, Echavarri-Guzman MA, Cerda-Flores RM (2009) Lead-, cadmium-, and arsenic-induced DNA damage in rat germinal cells. DNA Cell Biol 28:241–248

    CAS  PubMed  Google Scholar 

  49. Blanco A, Moyano R, Molina-Lopez AM, Blanco C, Flores-Acuna R, Garcia-Flores JRE, Spada M, Monterde JG (2010) Preneoplastic and neoplastic changes in the Leydig cells population in mice exposed to low doses of cadmium. Toxicol Ind Health 26:451–457

    CAS  PubMed  Google Scholar 

  50. Shimada H, Narumi R, Nagano M, Yasutake A, Waalkes MP, Imamura Y (2009) Strain differences in cadmium-induced testicular toxicity in inbred Wistar-Imamichi and Fischer 344 rats. Arch Toxicol 83:647–652

    CAS  PubMed  Google Scholar 

  51. Al-Azemi M, Omu FE, Kehinde EO, Anim JT, Oriowo MA, Omu AE (2010) Lithium protects against toxic effects of cadmium in the rat testes. J Assist Reprod Genet 27:469–476

    PubMed Central  PubMed  Google Scholar 

  52. Eybl V, Kotyzova D (2010) Protective effects of manganese in cadmium- induced hepatic oxidative damage, changes in cadmium distribution and trace elements level in mice. Interdiscip Toxicol 3:68–72

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Honda A, Komuro H, Shimada A, Hasegawa T, Seko Y, Nagase H, Hozumi I, Inuzuka T, Hara H, Fujiwara Y, Satoh M (2010) Attentuation of cadmium induced testicular injury in metallothionein-III null mice. Life Sci 87:545–550

    CAS  PubMed  Google Scholar 

  54. Ji YL, Wang H, Meng C, Zhao XF, Zhang C, Zhang Y, Zhao M, Chen YH, Meng XH, Xe DX (2012) Melatonin alleviates cadmium-induced cellular stress and germ cell apoptosis in testes. J Pineal Res 52:71–79

    CAS  PubMed  Google Scholar 

  55. Wang L, Xu T, Lei WW, Li YJ, Xuan RJ, Ma JJ (2011) Cadmium-induced oxidative stress and apoptotic changes in the testis of freshwater crab, Sinopotamon henansense. PLoS One 6:27583

    Google Scholar 

  56. Jana S, Sahana SS (1988) Effect of copper, cadmium and chromium cations on the fresh water fish Clarias batrachus. Physiol Bohemoslov 37:79–82

    CAS  PubMed  Google Scholar 

  57. Stacey NH, Wong KL, Klaassen CD (1983) Protective effects of chromium on the toxicity of cadmium in vivo. Toxicology 28:147–153

    CAS  PubMed  Google Scholar 

  58. Murthy RC, Saxena DK, Gupta SK, Chandra SV (1991) Ultrastructural observations in testicular tissue of chromium-treated rats. Reprod Toxicol 5:443–447

    CAS  PubMed  Google Scholar 

  59. Elbetieha A, Al-Hamood MH (1997) Long-term exposure of male and female mice to trivalent and hexavalent chromium compounds: effect of fertility. Toxicology 116:39–47

    CAS  PubMed  Google Scholar 

  60. Cheng RY, Alvord WG, Powell D, Kasprzak KS, Anderson LM (2002) Microarray array analysis of altered gene expression in the TM4 Sertoli-like cell line exposed to chromium(III) chloride. Reprod Toxicol 16:223–236

    CAS  PubMed  Google Scholar 

  61. de Lourdes Pereira M, Santos TM, Garcia e Costa F, de Jesus JP (2004) Functional changes of mice Sertoli cells induced by Cr(V). Cell Biol Toxicol 20:285–291

    PubMed  Google Scholar 

  62. Aruldhas MM, Subramanian S, Sekar P, Vengatesh G, Chandrahasan G, Govindarajulu P, Akbarsha MA (2005) Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: study on a non-human primate (Macaca radiate Geoffroy). Hum Reprod 20:2801–2813

    CAS  PubMed  Google Scholar 

  63. Chorvativikova D, Ginter E, Kosinova A, Zloch Z (1991) Effect of vitamins C and E on toxicity and mutagenicity of hexavalent chromium in rat and guinea pig. Mut Res 262:41–46

    Google Scholar 

  64. Bano Y, Hasan M (1990) Histopathological lesions in the body organs of cat fish (Heteropneustes fossilis) followed by mercury intoxication. J Environ Sci Health B 25:67–85

    CAS  PubMed  Google Scholar 

  65. Mohamed MK, Burbacher TM, Mottet NK (1987) Effect of methyl mercury on testicular functions in Macaca fascicularis monkeys. Pharmacol Toxicol 60:29–36

    CAS  PubMed  Google Scholar 

  66. Maretta M, Marettova E, Skrobanek P, Ledec M (1995) Effect of mercury on the seminiferous epithelium of the fowl testis. Acta Vet Hung 43:153–161

    CAS  PubMed  Google Scholar 

  67. Ernst E, Moller-Madsen B, Danscher G (1991) Ultrastructural demonstration of mercury in Sertoli and Leydig cells of the rat following methyl mercuric chloride or mercuric chloride treatment. Reprod Toxicol 5:205–209

    CAS  PubMed  Google Scholar 

  68. Eto K, Yasutake A, Miyamoto K, Tokunaga H, Otsuka Y (1997) Chronic effects of methyl mercury in rats. II. Pathological aspects. Tohoku J Exp Med 182:197–205

    CAS  PubMed  Google Scholar 

  69. Orisakwe OE, Afonne OJ, Nwobodo E, Asomugha L, Dioka CE (2001) Low-dose mercury induces testicular damage protected by zinc in mice. Eur J Obstet Gynecol Reprod Biol 95:92–96

    CAS  PubMed  Google Scholar 

  70. Massanyi P, Lukac N, Slivkova J, Kovacik J, Makaevich AV, Chrenek P, Toman R, Forgacs Z, Somosy Z, Stawarz R, Formicki G (2007) Mercury induced alterations in rat kidneys and testis in vivo. J Environ Sci Health A 42(865):870

    Google Scholar 

  71. Bonde JP (2010) Male reproductive organs are at risk from environmental hazards. Asian J Androl 12:152–156

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Boujbiha MA, Hamden K, Guermazi F, Bouslama A, Omezzine A, Kammou A, El Feki A (2009) Testicular toxicity in mercuric chloride treated rats: association with oxidative stress. Reprod Toxicol 28:81–89

    CAS  PubMed  Google Scholar 

  73. Rao MV, Sharma PS (2001) Protective effects of vitamin E against mercuric chloride reproductive toxicity in male mice. Reprod Toxicol 15:705–712

    CAS  PubMed  Google Scholar 

  74. Kalender S, Uzun FG, Demir F, Uzunhisarcikli M, Aslanturk A (2013) Mercuric chloride-induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E. Food Chem Toxicol 55:456–462

    CAS  PubMed  Google Scholar 

  75. Ayinde OC, Ogunnowo S, Ogedegbe RA (2012) Influence of vitamin and vitamin E on testicular zinc content and testicular toxicity in lead exposed albino rats. BMC Pharmacol Toxicol 13:13–17

    Google Scholar 

  76. Pandya C, Pillai P, Nampoothiri LP, Bhatt N, Gupta S, Gupta S (2012) Effect of lead and cadmium co exposure on testicular steroid metabolism and antioxidant system of adult male rats. Andrologia 44(Suppl i):813–822

    PubMed  Google Scholar 

  77. Massanyi P, Lukac N, Makarevich AV, Chrenek P, Forgacs Z, Zakrzewski M, Stawarz R, Toman R, Lazor P, Flesarova S (2007) Lead-induced alterations in rat kidneys and testes in vivo. J Environ Sci Health A 2007:671–676

    Google Scholar 

  78. Wang MZ, Jia XY (2009) Low levels of lead exposure induce oxidative damage and DNA damage in the testes of the frog, Rana nigromaculata. Ecotoxicology 16:94–99

    Google Scholar 

  79. Rafuque M, Pervez S, Tahir F (2010) Protective effects of zinc over lead toxicity on testes. J Coll Physicians Surg Pak 20:377–381

    Google Scholar 

  80. Yu T, Li Z, Wang X, Niu K, Xiao J, Li B (2010) Effects of lead exposure on male sexual hormone. Wei Sheng Yan Jiu 39:413–415

    PubMed  Google Scholar 

  81. El Shafai A, Zohdy N, El Mulls K, Hassan M, Morad N (2011) Light and electron microscopic study of the toxic effect of prolonged lead exposure on the seminiferous tubules of albino rats and the possible protective effect of ascorbic acid. Food Chem Toxicol 49:734–743

    PubMed  Google Scholar 

  82. Shaban El-Neweshy M, Said El-Sayed Y (2011) Influence of vitamin C supplementation on lead-induced histopathological alterations in male rats. Exp Toxicol Pathol 63:221–227

    CAS  PubMed  Google Scholar 

  83. Omura M, Tanaka A, Hirata M, Zhao M, Makita Y, Inoue N, Gotoh K, Ishinishi N (1996) Testicular toxicity of gallium arsenide, indium arsenide and arsenic oxide in rats by repetitive intratracheal instillation. Fundam Appl Toxicol 32:72–78

    CAS  PubMed  Google Scholar 

  84. Chang SI, Jin B, Youn P, Park C, Park JD, Ryu DY (2007) Arsenic-induced toxicity and the protective role of ascorbic acid in mouse testis. Toxicol Appl Pharmacol 218:196–203

    CAS  PubMed  Google Scholar 

  85. DuMond JW Jr, Singh KP (2007) Gene expression changes and induction of cell proliferation by chronic exposure to arsenic of mouse testicular Leydig cells. J Toxicol Environ Health A 70:1150–1154

    CAS  PubMed  Google Scholar 

  86. Sanghamitra S, Hazra J, Upadhyay SN, Singh RK, Amal RC (2008) Arsenic-induced toxicity in testicular tissue of mice. Indian J Physiol Pharmacol 52:84–90

    PubMed  Google Scholar 

  87. Bombard EM, Cohen SM, Gelbke HP, Williams GM (2012) Evaluation of the male reproductive toxicity of gallium arsenide. Regul Toxicol Pharmacol 64:77–86

    Google Scholar 

  88. Li Y, Wang M, Piao F, Wang X (2012) Subchronic exposure to arsenic inhibits spermatogenesis and down regulates the expression of ddx3y in testis and epididymis of mice. Toxicol Sci 128:482–489

    CAS  PubMed  Google Scholar 

  89. Sharma G, Kumar M (2012) Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment. J Environ Sci (China) 24:2159–2165

    CAS  Google Scholar 

  90. Zeng Q, Zhou B, Feng W, Wang YX, Liu AL, Yue J, Li YF, Lu WQ (2013) Associations of urinary metal concentrations and circulating testosterone in Chinese men. Reprod Toxicol 41:109–114

    CAS  PubMed  Google Scholar 

  91. Gunnarsson D, Svensson M, Selstam G, Nordberg G (2004) Pronounced induction of testicular PGF(2 alpha) and suppression of testosterone by cadmium-prevention by zinc. Toxicology 200:49–58

    CAS  PubMed  Google Scholar 

  92. Shimada H, Bare RM, Hochadel JF, Waalkes MP (1997) Testosterone pretreatment mitigates cadmium toxicity in male C57 mice but not in C3H mice. Toxicology 116:183–191

    CAS  PubMed  Google Scholar 

  93. Hosni H, Selim O, Abbas M, Fathy A (2013) Semen quality and reproductive endocrinal function related to blood lead levels in infertile painters. Andrologia 45:120–127

    CAS  PubMed  Google Scholar 

  94. Heath JC, Abdelmageed Y, Braden TD, Goyal HO (2012) The effect of chronic ingestion of mercuric chloride on fertility and testosterone levels in male Sprague Dawley rats. J Biomed Biotechnol 2012:815186

    PubMed Central  PubMed  Google Scholar 

  95. Marouani N, Tebourbi O, Mahjoub S, Yacoubi MT, Sakly M, Benkhalifa M, Rhouma KB (2012) Effect of hexavalent chromium on reproductive functions of male adult rats. Reprod Biol 12:119–133

    PubMed  Google Scholar 

  96. IARC (1997) IARC monographs on the evaluation of carcinogenic risks to humans. International Agency for Research on Cancer (IARC), Lyon, p 69

    Google Scholar 

  97. Davis NJ, Price HCO, Connor RW, Fernando R, Rowland AS, Morgan DL (2001) Mercury vapour and female reproductive toxicity. Toxicol Sci 59:291–296

    CAS  PubMed  Google Scholar 

  98. Ehrenstein C, Shu P, Wickenheiser EB, Hirner AV, Dolfen M, Emons H, Obe G (2002) Methyl mercury uptake and associations with the induction of chromosomal aberrations in Chinese hamster ovary (CHO) cells. Chem Biol Interact 141:259–274

    CAS  PubMed  Google Scholar 

  99. Khan AT, Atkinson A, Graham TC, Thompson SJ, Ali S, Shireen KF (2004) Effect of inorganic mercury on reproductive performance of mice. Food Chem Toxicol 42:571–577

    CAS  PubMed  Google Scholar 

  100. Al-Saleh I, Shinwari N, Al-Amodi M (2009) Accumulation of mercury in ovaries of mice after application of skin-lightening creams. Biol Trace Elem Res 131:43–54

    CAS  PubMed  Google Scholar 

  101. Kolesarova A, Roychoudhury S, Slivkova J, Sirotkin A, Capcarova M, Massanyi P (2010) In vitro study on the effects of lead and mercury on procine ovarian granulose cells. J Environ Sci Health 45:320–331

    CAS  Google Scholar 

  102. Massanyi P, Lukac N, Uhrin V, Toman R, Pivko J, Rafay J, Forzacs Z, Somosy Z (2007) Female reproductive toxicity of cadmium. Acta Biol Hung 58:287–299

    CAS  PubMed  Google Scholar 

  103. Nad P, Massany P, Skalicka M, Korenekova B, Cigankova V, Almasiova V (2007) The effect of cadmium in combination with zinc and selenium on ovarian structure in Japanese quails. J Environ Sci Health A 42:2017–2022

    CAS  Google Scholar 

  104. Zhang W, Jia H (2007) Effect and mechanism of cadmium on the progesterone synthesis of ovaries. Toxicology 239:204–212

    CAS  PubMed  Google Scholar 

  105. Wan X, Zhu J, Zhu Y, Zhu Y, Ma X, Zheng Y, Wang F, Liu Z, Zhang T (2010) Rat ovarian follicles bioassay reveals adverse effects of cadmium chloride (CdCl2) exposure on follicle development and oocyte maturation. Toxicol Ind Health 26:609–618

    CAS  PubMed  Google Scholar 

  106. Angenard G, Muczynski V, Coffigny H, Pairault C, Duquenne C, Frydman R, Habert R, Rouiller-Fabre V, Livera G (2010) Cadmium increase human foetal germ cell apoptosis. Environ Health Perspect 118:331–337

    CAS  PubMed Central  PubMed  Google Scholar 

  107. Revathi P, Vasanthi LA, Munuswami N (2011) Effect of cadmium on ovarian development in the freshwater prawn Macrobrachium rosenbergii (De Man). Ecotoxicol Environ Saf 74:623–629

    CAS  PubMed  Google Scholar 

  108. Yang S, Zhang Z, He J, Li J, Zhang J, Xing H, Xu S (2012) Ovarian toxicity induced by dietary cadmium in hen. Biol Trace Elem Res 148:53–60

    CAS  PubMed  Google Scholar 

  109. Tsuzuki K, Sugiyama M, Haramaki N (1994) DNA single-strand breaks and cytotoxicity induced by chromate(VI), cadmium(II), and mercury(II) in hydrogen peroxide resistant cell lines. Environ Health Perspect 102:341–342

    CAS  PubMed Central  PubMed  Google Scholar 

  110. Ostergards DR (1970) The physiology and clinical importance of amniotic fluid. A review. Obstet Gynecol Surv 25:297–319

    Google Scholar 

  111. Gundacker C, Hengstschlager M (2012) The role of placenta in foetal exposure to heavy metals. Wien Med Wochenschr 162:201–206

    PubMed  Google Scholar 

  112. Odland JO, Nieboer E, Romanova N, Hofoss D, Thomassen Y (2003) Intercommunity and temporal variation of eleven essential and five toxic elements in human placentas from deliveries in thirteen arctic and sub-arctic areas of Russia and Norway. J Environ Monitor 5:166–174

    CAS  Google Scholar 

  113. McDermott S, Bao W, Marjorie Aelionc Cai B, Lawson A (2012) When are foetuses of young children most susceptible to soil metal concentrations of arsenic, lead and mercury? Spatiotemporal Epidemiol 3:265–272

    Google Scholar 

  114. Goyer RA (1990) Transplacental transport of lead. Environ Health Perspect 89:101–105

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Al-Saleh I, Shinwari N, Mashhour A, Mohamed Gel D, Rabah A (2011) Heavy metals (lead, cadmium and mercury) in maternal cord blood and placenta of healthy women. Int J Hyg Environ Health 214:79–101

    CAS  PubMed  Google Scholar 

  116. Reichrtova E, Dorociak F, Plakovikova L (1998) Sites of lead and nickel accumulation in the placental tissue. Hum Exp Toxicol 17:176–181

    CAS  PubMed  Google Scholar 

  117. Ask K, Akesson A, Berglund M, Vahter M (2002) Inorganic mercury and methyl mercury in placenta of Swedish women. Environ Health Perspect 110:523–526

    CAS  PubMed Central  PubMed  Google Scholar 

  118. Stasenko S, Bradford EM, Piasek M, Henson MC, Varnai VM, Jurasovic J, Kusek V (2010) Metals in human placenta: focus on the effects of cadmium on steroid hormones and leptin. J Appl Toxicol 30:242–253

    CAS  PubMed  Google Scholar 

  119. Chen YW, Yang CY, Huang DZ, Leung YM, Liu SH (2009) Heavy metals, islet function and diabetes development. Islets 1:169–176

    PubMed  Google Scholar 

  120. Lei LJ, Jin TY, Zhou YF (2005) The toxic effects of cadmium on pancreas. Zhonghua Lao Domg Wei Sheng Zhi Ye Bing Za Zhi 23:45–49

    CAS  Google Scholar 

  121. Lei LJ, Jin TY, Zhou YF (2007) Insulin expression in rats exposed to cadmium. Biomed Environ Sci 20:295–301

    CAS  PubMed  Google Scholar 

  122. Singh N, Rana SVS (2009) Effect of insulin on arsenic toxicity in diabetic rats—liver function studies. Biol Trace Elem Res 132:215–226

    CAS  PubMed  Google Scholar 

  123. Yen CC, Lu FJ, Huang CF, Chen WK, Liu SH, Lin-Shiau SY (2007) The dibetogenic effects of the combination of humic acid and arsenic: in vitro and in vivo studies. Toxicol Lett 172:91–105

    CAS  PubMed  Google Scholar 

  124. Fu J, Woods CG, Yehuda-Shnaidman E, Zhang Q, Wong V, Collins S, Sun G, Anderson ME, Pi J (2010) Low-level arsenic impairs glucose-stimulated insulin secretion in pancreatic beta cells: involvement of cellular adaptive response to oxidative stress. Environ Health Perspect 118(6):864–870

    CAS  PubMed Central  PubMed  Google Scholar 

  125. Diaz-Villasenor A, Sanchez-Soto MC, Cebrian ME, Ostrosky-Wegman P, Hiriart M (2006) Sodium arsenite impairs insulin secretion and transcription in pancreatic B cells. Toxicol Appl Pharmacol 214:30–34

    CAS  PubMed  Google Scholar 

  126. Lu TH, Su CC, Chen YW, Yang CY, Wu CC, Hung DZ, Chen CH, Cheng PW, Liu SH, Hunag CF (2011) Arsenic induces pancreatic β-cell apoptosis via the oxidative stress-regulated mitochondria dependent and endoplasmic reticulum stress- triggered signaling pathways. Toxicol Lett 201:15–26

    CAS  PubMed  Google Scholar 

  127. Chen YW, Huang CF, Tsai KS, Yang RS, Yen CC, Yang C, Lin-Shiau SY, Liu SH (2006) Methylmercury induces pancreatic beta-cell apoptosis and dysfunction. Chem Res Toxicol 19:1080–1085

    CAS  PubMed  Google Scholar 

  128. Yang B, Fu J, Zheng H, Xue P, Yarborough K, Woods CG, Hou Y, Zhang Q, Anderson ME, Pi J (2012) Deficiency in the nuclear factor E2-related factor 2 renders pancreatic β-cell vulnerable to arsenic-induced cell damage. Toxicol Appl Pharmacol 264:315–323

    CAS  PubMed Central  PubMed  Google Scholar 

  129. Lafuente A, Gonzalez-Carraced A, Romero A, Cabaleiro T, Esquifino Al (2005) Toxic effects of cadmium on the regulatory mechanisms of dopamine and serotonin on prolactin secretion in adult male rats. Toxicol Lett 155:87–96

  130. Piasek M, Laskey JW (1999) Effect of in?vitro cadmium exposure on ovarian steroidogenesis in rats. J Appl Toxicol 19:211–217

    CAS  PubMed  Google Scholar 

  131. Smida AD, Valderrama XP, Agostini MC, Furlan MA, Chedrese J (2004) Cadmium stimulates transcription of the cytochrome p450 side chain cleavage gene in genetically modified stable procine granulosa cells. Biol Reprod 70:25–31

    CAS  PubMed  Google Scholar 

  132. Agusa T, Kunito T, Iwata H, Monirith I, Chamnan C, Tana TS, Subramanian A, Tanabe S (2007) Mercury in hair and blood from residents of Phnom Penh (Cambodia) and possible effect on serum hormone levels. Chemosphere 68:590–596

    CAS  PubMed  Google Scholar 

  133. Paksy K, Gati I, Naray M, Rajczy K (2001) Lead accumulation in the human ovarian follicular fluid and in?vitro effect of lead on progesterone production by cultured human ovarian granulosa cells. J Toxicol Environ Health A 62:359–366

    CAS  PubMed  Google Scholar 

  134. Ronis MJ, Badger TM, Shema SJ, Roberson PK, Shaikh F (1996) Reproductive toxicity and growth effects in rats exposed to lead at different periods during development. Toxicol Appl Pharmacol 136:361–371

    CAS  PubMed  Google Scholar 

  135. Ronis MJ, Gandy J, Badger T (1998) Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to lead. J Toxicol Environ Health A 54:77–99

    CAS  PubMed  Google Scholar 

  136. Sokol RZ, Berman N (1991) The effect of age and exposure on lead-induced testicular toxicity. Toxicology 69:269–278

    CAS  PubMed  Google Scholar 

  137. Rodriguez EM, Medesani DA, Fingerman M (2007) Endocrine disruption in crustaceans due to pollutants: a review. Comp Biochem Physiol A 146:661–671

    Google Scholar 

  138. Novillo A, Won SJ, Li C, Callard IP (2005) Changes in nuclear receptor and vitellogenin gene expression in response to steroids and heavy metals in Caenorhabditis elegans. Integr Comp Biol 45:61–71

    CAS  PubMed  Google Scholar 

  139. Schantz SL, Widholm JJ (2001) Cognitive effects of endocrine-disrupting chemicals in animals. Environ Health Perspect 109:1197–1206

    CAS  PubMed Central  PubMed  Google Scholar 

  140. Lizardo-Daudt HM, Bains OS, Singh CR, Kennedy CJ (2008) Cadmium chloride-induced disruption of testicular steroidogenesis in rainbow trout, Oncorhynchus mykiss. Arch Environ Contam Toxicol 55:103–110

    CAS  PubMed  Google Scholar 

  141. Yoon S, Han SS, Rana SVS (2008) Molecular markers of heavy metal toxicity—a new paradigm for health risk assessment. J Environ Biol 29:1–14

    CAS  PubMed  Google Scholar 

  142. Dalton TP, Miller ML, Wu X, Menon A, Cianciolo E, McKinnon RA, Smith PW, Robinson LJ, Nebert DW (2000) Refining the mouse chromosomal location of Cd, the major gene associated with susceptibility to cadmium-induced testicular necrosis. Pharmacogenetics 10:141–151

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

I am thankful to my colleagues Dr Y Verma and Mr Nitin Sharma for their skilful assistance in the preparation of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. V. S. Rana.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rana, S.V.S. Perspectives in Endocrine Toxicity of Heavy Metals—A Review. Biol Trace Elem Res 160, 1–14 (2014). https://doi.org/10.1007/s12011-014-0023-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0023-7

Keywords

Navigation