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.
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
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
Friberg L, Nordberg GF, Vouk V (1986) Handbook on the toxicology of metals, 2nd ed. Volume 1: general aspects. Elsevier, Amsterdam, New York, Oxford
Goyer RA, Klaassen CD, Waalkes MP (1995) Metal toxicology. Academic, San Diego, New York, London, Sydney, Tokyo, Toronto
Hughes MN (1972) The inorganic chemistry of biological processes. Wiley, New York
Hart DT, Borowitz JL (1974) Adrenal catecholamine release by divalent mercury and cadmium. Arch Int Pharmacodyn Ther 209:94–99
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
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
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
Barregard L, Lindstedt G, Schutz A, Sallsten G (1994) Endocrine function in mercury exposed chloralkali workers. Occup Environ Med 51:536–540
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
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
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
Lafuente A, Esquifino A (1999) Cadmium effects on hypothalamic activity and pituitary hormone secretion in the male. Toxicol Lett 110:209–218
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
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
Sandhu N, Vijayan MM (2011) Cadmium-mediated disruption of cortisol biosynthesis involves suppression of corticosteroidogenic genes in rainbow trout. Aquat Toxicol 103:92–100
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
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
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
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
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
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
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
Doumouchtsis KK, Doumouschtsis SK, Doumouchtsis EK, Perrea DN (2009) The effect of lead intoxication on endocrine functions. Endocrinol Investig 32:175–183
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
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
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
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
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
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
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
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
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
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
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
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
Danielsson BR, Dencker L, Lindgren A, Tjalve H (1984) Accumulation of toxic metals in male reproductive organs. Arch Toxicol Suppl 7:177–180
Friberg L, Piscator M, Nordberg GF (1974) Cadmium in the environment, 2nd edn. CRC Press, Cleveland, pp 37–53
Goyer RA, Liu J, Waalkes MP (2004) Cadmium and cancer of prostate and testis. Biometals 17:555–558
Martynowicz H, Skoczynska A, Karczmarek-Wdowiak B, Andrzejak R (2005) Effects of cadmium on testis function. Med Pr 56:167–174
Bertin G, Averbeck D (2006) Cadmium: cellular effects, modifications of biomolecules, modulation of DNA repair and genotoxic consequences (a review). Biochimie 88:1549–1559
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
Takiguchi M, Yoshihara S (2006) New aspects of cadmium as endocrine disruptor. Environ Sci 13:107–116
Siu ER, Mruk DD, Porto CS, Cheng CY (2009) Cadmium-induced testicular injury. Toxicol Appl Pharmacol 238:240–249
Thompson J, Bannigan J (2008) Cadmium: toxic effects on the reproductive system and the embryo. Reprod Toxicol 25:304–315
Burukoglu D, Baycu C (2008) Protective effects of zinc on testis of cadmium treated rats. Bull Environ Contam Toxicol 81:521–524
Liu J, Qu W, Kadiska MB (2009) Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol 1238:209–214
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
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
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
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
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
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
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
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
Jana S, Sahana SS (1988) Effect of copper, cadmium and chromium cations on the fresh water fish Clarias batrachus. Physiol Bohemoslov 37:79–82
Stacey NH, Wong KL, Klaassen CD (1983) Protective effects of chromium on the toxicity of cadmium in vivo. Toxicology 28:147–153
Murthy RC, Saxena DK, Gupta SK, Chandra SV (1991) Ultrastructural observations in testicular tissue of chromium-treated rats. Reprod Toxicol 5:443–447
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
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
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
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
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
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
Mohamed MK, Burbacher TM, Mottet NK (1987) Effect of methyl mercury on testicular functions in Macaca fascicularis monkeys. Pharmacol Toxicol 60:29–36
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
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
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
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
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
Bonde JP (2010) Male reproductive organs are at risk from environmental hazards. Asian J Androl 12:152–156
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
Rao MV, Sharma PS (2001) Protective effects of vitamin E against mercuric chloride reproductive toxicity in male mice. Reprod Toxicol 15:705–712
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
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
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
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
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
Rafuque M, Pervez S, Tahir F (2010) Protective effects of zinc over lead toxicity on testes. J Coll Physicians Surg Pak 20:377–381
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
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
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
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
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
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
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
Bombard EM, Cohen SM, Gelbke HP, Williams GM (2012) Evaluation of the male reproductive toxicity of gallium arsenide. Regul Toxicol Pharmacol 64:77–86
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
Sharma G, Kumar M (2012) Antioxidant and modulatory role of Chlorophytum borivilianum against arsenic induced testicular impairment. J Environ Sci (China) 24:2159–2165
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
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
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
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
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
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
IARC (1997) IARC monographs on the evaluation of carcinogenic risks to humans. International Agency for Research on Cancer (IARC), Lyon, p 69
Davis NJ, Price HCO, Connor RW, Fernando R, Rowland AS, Morgan DL (2001) Mercury vapour and female reproductive toxicity. Toxicol Sci 59:291–296
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
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
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
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
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
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
Zhang W, Jia H (2007) Effect and mechanism of cadmium on the progesterone synthesis of ovaries. Toxicology 239:204–212
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
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
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
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
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
Ostergards DR (1970) The physiology and clinical importance of amniotic fluid. A review. Obstet Gynecol Surv 25:297–319
Gundacker C, Hengstschlager M (2012) The role of placenta in foetal exposure to heavy metals. Wien Med Wochenschr 162:201–206
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
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
Goyer RA (1990) Transplacental transport of lead. Environ Health Perspect 89:101–105
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
Reichrtova E, Dorociak F, Plakovikova L (1998) Sites of lead and nickel accumulation in the placental tissue. Hum Exp Toxicol 17:176–181
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
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
Chen YW, Yang CY, Huang DZ, Leung YM, Liu SH (2009) Heavy metals, islet function and diabetes development. Islets 1:169–176
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
Lei LJ, Jin TY, Zhou YF (2007) Insulin expression in rats exposed to cadmium. Biomed Environ Sci 20:295–301
Singh N, Rana SVS (2009) Effect of insulin on arsenic toxicity in diabetic rats—liver function studies. Biol Trace Elem Res 132:215–226
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
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
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
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
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
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
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
Piasek M, Laskey JW (1999) Effect of in?vitro cadmium exposure on ovarian steroidogenesis in rats. J Appl Toxicol 19:211–217
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
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
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
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
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
Sokol RZ, Berman N (1991) The effect of age and exposure on lead-induced testicular toxicity. Toxicology 69:269–278
Rodriguez EM, Medesani DA, Fingerman M (2007) Endocrine disruption in crustaceans due to pollutants: a review. Comp Biochem Physiol A 146:661–671
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
Schantz SL, Widholm JJ (2001) Cognitive effects of endocrine-disrupting chemicals in animals. Environ Health Perspect 109:1197–1206
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
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
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
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
Corresponding author
Rights and permissions
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-014-0023-7