Heavy Metals as Endocrine-Disrupting Chemicals

  • Cheryl A. Dyer
Part of the Contemporary Endocrinology book series (COE)


Heavy Metal Estrogen Receptor Endocrine Disruption Toxicol Environ Health Uranyl Nitrate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Colborn T, vom Saal FS, Soto AM. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ Health Perspect 1993;101:378–84.PubMedGoogle Scholar
  2. 2.
    Jarup L. Hazards of heavy metal contamination. Br Med Bull 2003;68:167–82.PubMedGoogle Scholar
  3. 3.
    Medici N, Minucci S, Nigro V, Abbondanza C, Armetta I, Molinari AM, Puca GA. Metal binding sites of the estradiol receptor from calf uterus and their possible role in the regulation of receptor function. Biochemistry 1989;28:212–19.PubMedGoogle Scholar
  4. 4.
    Predki PF, Sarkar B. Effect of replacement of zinc finger zinc on estrogen receptor DNA interactions. J Biol Chem 1992;267:5842–46.PubMedGoogle Scholar
  5. 5.
    Martin MB, Reiter R, Pham T, Avellanet YR, Camara J, Lahm M, Pentecost E, Pratap K, Gilmore BA, Divekar S, Dagata RS, Bull JL, Stoica A. Estrogen-like activity of metals in Mcf-7 breast cancer cells. Endocrinology 2003;144:2425–36.PubMedGoogle Scholar
  6. 6.
    Nesatyy VJ, Rutishauser BV, Eggen RIL, Suter JF. Identification of the estrogen receptor Cd-binding sites by chemical modification. Analyst 2005;130:1087–97.PubMedGoogle Scholar
  7. 7.
    Nesatyy VI, Ammann AA, Rutishauser BV, Suter MJF. Effect of cadmium on the interaction of 17β-estradiol with the rainbow trout estrogen receptor. Environ Sci Technol 2006;40:1358–63.PubMedGoogle Scholar
  8. 8.
    Johnson MD, Kenney N, Stoica A, Hilakivi-Clarke L, Singh B, Chepko G, Clarke R, Sholler PF, Lirio AA, Foss C, Reiter R, Trock B, Paik S, Martin MB. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med 2003;9:1081–84.PubMedGoogle Scholar
  9. 9.
    Safe S. Cadmium’s disguise dupes the estrogen receptor. Nat Med 2003;9:1000–1.PubMedGoogle Scholar
  10. 10.
    Darbre PD. Metalloestrogens: an emerging class of inorganic xenoestrogens with potential to add to the oestrogenic burden of the human breast. J Appl Toxicol 2006;26:191–7.PubMedGoogle Scholar
  11. 11.
    Mandal BK, Suzuki KT. Arsenic round the world: a review. Talanta 2002;58:201–35.Google Scholar
  12. 12.
    Waxman S, Anderson KC. History of the development of arsenic derivatives in cancer therapy. Oncologist 2001;6(Suppl 2):3–10.PubMedGoogle Scholar
  13. 13.
    Klaassen CD. Heavy metals and heavy-metal antagonists. In: Brunton LL, ed. Goodman & Gilman the Pharmacological Basis of Therapeutics, 11th ed. New York: McGraw-Hill, 2006:1753–75.Google Scholar
  14. 14.
    Kwon E, Zhang H, Wang Z, Jhangri GS, Lu X, Fok N, Gabos S, Li XF, Le XC. Arsenic on the hands of children after playing in playgrounds. Environ Health Perspect 2004;112:1375–80.PubMedGoogle Scholar
  15. 15.
    Tapio S, Grosche B. Arsenic in the aetiology of cancer. Mutat Res 2006;612:215–46.PubMedGoogle Scholar
  16. 16.
    U.S. Environmental Protection Agency. Arsenic in drinking water. Scholar
  17. 17.
    Frost FJ, Muller T, Petersen HV, Thomson B, Tollestrup K. Identifying US populations for the study of health effects related to drinking water arsenic. J Expo Anal Environ Epidemiol 2003;13:231–39.PubMedGoogle Scholar
  18. 18.
    Jana K, Jana S, Samanta PK. Effects of chronic exposure to sodium arsenite on hypothalamo-pituitary-testicular activities in adult rats: possible an estrogenic mode of action. Reprod Biol Endocrinol 2006;4:9.PubMedGoogle Scholar
  19. 19.
    Waalkes MP, Keefer LK, Diwan BA. Induction of proliferative lesions of the uterus, testes, and liver in Swiss mice given repeated injections of sodium arsenate: possible estrogenic mode of action. Toxicol Appl Pharmacol 2000;166:24–35.PubMedGoogle Scholar
  20. 20.
    Waalkes MP, Ward JM, Liu J, Diwan BA. Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice. Toxicol Appl Pharmacol 2003;186:7–17.PubMedGoogle Scholar
  21. 21.
    Waalkes MP, Liu J, Ward JM, Powell DA, Diwan BA. Urogenital carcinogenesis in female CD1 mice induced by in utero arsenic exposure is exacerbated by postnatal diethylstilbestrol. Cancer Res 2006;66:1337–45.PubMedGoogle Scholar
  22. 22.
    Waalkes MP, Liu J, Ward JM, Diwan B. Enhanced urinary bladder and liver carcinogenesis in male CD1 mice exposed to transplancental inorganic arsenic and postnatal diethylstilbestrol or tamoxifen. Toxicol Appl Pharmacol 2006;May 16, Epub ahead of print.Google Scholar
  23. 23.
    Waalkes MP, Liu J, Chen H, Xie Y, Achanzar WE, Zhou YS, Cheng ML, Diwan BA. Estrogen signaling in livers of male mice with hepatocellular carcinoma induced by exposure to arsenic in utero. J Natl Cancer Inst 2004;96:466–74.Google Scholar
  24. 24.
    Chattopadhyay S, Ghosh S, Chaki S, Debnath J, Ghosh D. Effect of sodium arsenite on plasma levels of gonadotrophins and ovarian steroidogenesis in mature albino rats: duration-dependent response. J Toxicol Sci 1999;24:425–31.PubMedGoogle Scholar
  25. 25.
    Golub MS, Macintosh MS. Developmental and reproductive toxicity on inorganic arsenic: animal studies and human concerns. J Toxicol Environ Health B Crit Rev 1998;1:199–241.PubMedGoogle Scholar
  26. 26.
    Tseng GH. The potential biological mechanisms of arsenic – induced diabetes mellitus. Toxicol Appl Pharmacol 2004;197:67–83.PubMedGoogle Scholar
  27. 27.
    Tseng GH. Blackfoot disease and arsenic: a never-ending story. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2005;23:55–74.PubMedGoogle Scholar
  28. 28.
    Livingstone C, Collison M. Sex steroids and insulin resistance. Clin Sci (Lond) 2002;102:151–66.Google Scholar
  29. 29.
    Valko M, Morris H, Cronin MTD. Metals, toxicity and oxidative stress. Curr Med Chem 2005;12:1161–208.PubMedGoogle Scholar
  30. 30.
    Nordstrom S, Beckman L, Nordenson I. Occupational and environmental risks in and around a smelter in northern Sweden. V. Spontaneous abortion among female employees and decreased birth weight in their offspring. Hereditas 1979;90:291–6.PubMedGoogle Scholar
  31. 31.
    Tabacova S, Baird DD, Balabaeva Lolova LD, Petrov I. Placental arsenic and cadmium in relation to lipid peroxides and glutathione levels in maternal-infant pairs from a copper smelter area. Placenta 1994;15:873–1.PubMedGoogle Scholar
  32. 32.
    Soto AM, Maffini MV, Schaeberle CM, Sonnenschein C. Strengths and weaknesses of in vitro assays for estrogenic and androgenic activity. Best Pract Res Clin Endocrinol Metab 2006;20:15–33.PubMedGoogle Scholar
  33. 33.
    Stoica A, Pentecost E, Martin MB. Effects of arsenite on estrogen receptor-α expression and activity in MCF-7 breast cancer cells. Endocrinology 2000;141:3595–602.PubMedGoogle Scholar
  34. 34.
    Choe SY, Kim SJ, Kim HG, Lee JH, Choi Y, Lee H, Kim Y. Evaluation of estrogenicity of major heavy metals. Sci Total Environ 2003;312:15–21.PubMedGoogle Scholar
  35. 35.
    Chow SKY, Chan JYW, Fung KP. Suppression of cell proliferation and regulation of estrogen receptor α signal pathway by arsenic trioxide on human breast cancer MCF-7 cells. J Endocrinol 2004;182:325–7.Google Scholar
  36. 36.
    Kitchin KT, Wallace K. Arsenite binding to synthetic peptides based on the Zn finger region and the estrogen binding region of the human estrogen receptor. Toxicol Appl Pharmacol 2005;206:66–72.PubMedGoogle Scholar
  37. 37.
    Kitchin KT, Wallace K. Arsenite binding to synthetic peptides: the effect of increasing length between two cysteines. J Biochem Mol Toxicol 2006;20:35–8.PubMedGoogle Scholar
  38. 38.
    Lopez S, Miyashita Y, Simons SS. Structurally based selective interaction of arsenite with steroid receptors. J Biol Chem 1990;265:16039–42.PubMedGoogle Scholar
  39. 39.
    Hamilton JW, Kaltreider RC, Bajenova OV, Ihnat MA, McCaffrey J, Turpie TW, Rowell EE, Oh J, Nemeth MJ, Pesce CA, Lariviere JP. Molecular basis for effects of carcinogenic heavy metals on inducible gene expression. Environ Health Perspect 1998;106:1005–5.PubMedGoogle Scholar
  40. 40.
    Kaltreider RC, Pesce CA, Ihnat MA, Lariviere JP, Hamilton JW. Differential effects of arsenic(III) and chromium(VI) on nuclear transcription factor binding. Mol Carcinog 1999;25:219–9.PubMedGoogle Scholar
  41. 41.
    Kaltreider RC, Davis AM, Lariviere JP, Hamilton JW. Arsenic alters the function of the glucocorticoid receptor as a transcription factor. Environ Health Perspect 2001;109:245–51.PubMedGoogle Scholar
  42. 42.
    Simons SS, Chakraborti PK, Cavanaugh AH. Arsenite and cadmium(II) as probes of glucocorticoid receptor structure and function. J Biol Chem 1990;265:1938–45.PubMedGoogle Scholar
  43. 43.
    Kitchin KT, Wallace K. Dissociation of arsenite-peptide complexes: triphasic nature, rate constants, half-lives and biological importance. J Biochem Mol Toxicol 2006;20:48–56.PubMedGoogle Scholar
  44. 44.
    Henson MC, Chedrese PJ. Endocrine disruption by cadmium, a common environmental toxicant with paradoxical effects on reproduction. Exp Biol Med (Maywood) 2004;229:383–92.Google Scholar
  45. 45.
    Nishijo M, Nakagawa H, Honda R, Tanebe K, Saito S, Teranishi H, Tawara K. Effects of maternal exposure to cadmium on pregnancy outcome and breast milk. Occup Environ Med 2002;59:394–97.PubMedGoogle Scholar
  46. 46.
    Zenzes MT, Krishnan S, Krishnan B, Zhang H, Casper RF. Cadmium accumulation in follicular fluid of women in in vitro fertilization-embryo transfer is higher in smokers. Fertil Steril 1995;64:599–603.PubMedGoogle Scholar
  47. 47.
    Piasek M, Blanusa M, Kostial K, Laskey JW. Placental cadmium and progesterone concentrations in cigarette smokers. Reprod Toxicol 2001;15:673–81.PubMedGoogle Scholar
  48. 48.
    Jolibois LS, Shi W, George WJ, Henson MC, Anderson MB. Cadmium accumulation and effects on progesterone release by cultured human trophoblast cells. Reprod Toxicol 1999;13:215–1.PubMedGoogle Scholar
  49. 49.
    Jolibois LS, Burow ME, Swan KF, George WJ, Anderson MB, Henson MC. Effects of cadmium on cell viability, trophoblastic development, and expression of low density lipoprotein receptor transcripts in cultured human placental cells. Reprod Toxicol 1999;13:473–80.PubMedGoogle Scholar
  50. 50.
    Kawai M, Swan KF, Green AE, Edwards DE, Anderson MB, Henson MC. Placental endocrine disruption induced by cadmium: effects on P450 cholesterol side-chain cleavage and 3β-hydroxysteroid dehydrogenase enzymes in cultured human trophoblasts. Biol Reprod 2002;67:178–83.PubMedGoogle Scholar
  51. 51.
    Yang K, Julan L, Rubio F, Sharma A, Guan H. Cadmium reduces 11β-hydroxysteroid dehydrogenase type 2 activity and expression in human placental trophoblast cells. Am J Physiol Endocrinol Metab 2006;290:E135–42.PubMedGoogle Scholar
  52. 52.
    Osmond C, Barker DJ. Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women. Environ Health Perspect 2000;108 (Suppl 3):545–3.PubMedGoogle Scholar
  53. 53.
    Cnattingius S. The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tob Res 2004;6(Suppl 2):S125–140.PubMedGoogle Scholar
  54. 54.
    Bush PG, Mayhew TM, Abramovich DR, Aggett PJ, Burke MD, Page KR. A quantitative study on the effects of maternal smoking on placental morphology and cadmium concentration. Placenta 2000;21:247–56.PubMedGoogle Scholar
  55. 55.
    Sun K, Yang K, Challis JRG. Regulation of 11β-hydroxysteroid dehydrogenase type 2 by progesterone, estrogen, and the cyclic adenosine 5’-monophosphate pathway in cultured human placental and chorionic trophoblasts. Biol Reprod 1998;58:1379–84.PubMedGoogle Scholar
  56. 56.
    Paksy K, Rajczy K, Forgacs Z, Lazar P, Bernard A, Gati I, Kaali G. Effect of cadmium on morphology and steroidogenesis of cultured human ovarian granulosa cells. J Appl Toxicol 1997;17:321–27.PubMedGoogle Scholar
  57. 57.
    Smida AD, Valderrame XP, Agostini MC, Furlan MA, Chedrese J. Cadmium stimulates transcription of the cytochrome P450 side chain cleavage gene in genetically modified stable porcine granulosa cells. Biol Reprod 2004;70:25–31.PubMedGoogle Scholar
  58. 58.
    Long GJ. The effect of cadmium on cytosolic free calcium, protein kinase C, and collagen synthesis in rat osteosarcoma (ROA 17/2.8) cells. Toxicol Appl Pharmacol 1997;143:189–95.PubMedGoogle Scholar
  59. 59.
    Piasek M, Laskey JW. Effect of in vitro cadmium exposure on ovarian steroidogenesis in rats. J Appl Toxicol 1999;19:211–17.PubMedGoogle Scholar
  60. 60.
    Piasek M, Laskey JW, Kostial K, Blanusa M. Assessment of steroid disruption using cultures of whole ovary and/or placenta in rat and in human placental tissue. Int Arch Occup Environ Health 2002;75(Suppl):S36–44.Google Scholar
  61. 61.
    Piasek M, Laskey JW. Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats. Reprod Toxicol 1994;8:495–507.PubMedGoogle Scholar
  62. 62.
    Waisberg M, Joseph P, Hale B, Beyersmann. Molecular and cellular mechanisms of cadmium carcinogenesis. Toxicology 2003;192:95–117.PubMedGoogle Scholar
  63. 63.
    Alsberg CL, Schwartze EW. Pharmacological action of Cd. Pharmacology 1919;13:504–9.Google Scholar
  64. 64.
    Chia SE, Xu B, Ong CN, Tsakok FM, Lee ST. Effect of cadmium and cigarette smoking on human semen quality. Int J Fertil Menopausal Stud 1994;39:292–8.PubMedGoogle Scholar
  65. 65.
    Al-Bader A, Omu AE, Dashti H. Chronic cadmium toxicity to sperm of heavy cigarette smokers: immunomodulation by zinc. Arch Androl 1999;43:135–40.PubMedGoogle Scholar
  66. 66.
    Yang JM, Arnush M, Chen QY, Wu XD, Pang B, Jiang XZ. Cadmium-induced damage to primary cultures of rat Leydig cells. Reprod Toxicol 2003;17:553–60.PubMedGoogle Scholar
  67. 67.
    Laskey JW, Phelps PV. Effect of cadmium and other metal cations on in vitro Leydig cell testosterone production. Toxicol Appl Pharmacol 1991;108:296–306.PubMedGoogle Scholar
  68. 68.
    Zeng X, Jin T, Zhou Y, Nordberg GF. Changes of serum sex hormone levels and MT mRNA expression in rats orally exposed to cadmium. Toxicol 2003;186:109–8.Google Scholar
  69. 69.
    Lafuente A, Marquez N, Perez-Lorenzo M, Pazo D, Esquifino AI. Pubertal and postpubertal cadmium exposure differentially affects the hypothalamic-pituitary-testicular axis function in the rat. Food Chem Toxicol 2000;38:913–23.PubMedGoogle Scholar
  70. 70.
    Zeng X, Jin T, Zhou Y. Alterations of serum hormone levels in male workers occupationally exposed to cadmium. J Toxicol Environ Health A 2002;65:513–21.PubMedGoogle Scholar
  71. 71.
    Jurasovic J, Cvitkovic P, Pizent A, Colak B, Telisman S. Semen quality and reproductive endocrine function with regard to blood cadmium in Croation male subjects. Biometals 2004;17:735–43.PubMedGoogle Scholar
  72. 72.
    Nagata C, Nagao Y, Shibuya C, Kashiki Y, Shimizu H. Urinary cadmium and serum levels of estrogens and androgens in postmenopausal Japanese women. Cancer Epidemiol Biomarkers Prev 2005;14:705–8.PubMedGoogle Scholar
  73. 73.
    Garcia-Morales P, Saceda M, Kenney N, Kim N, Salomon DS, Gottardis MM, Solomon HB, Sholler PF, Jordon VC, Martin MB. Effect of cadmium on estrogen receptor levels and estrogen-induced responses in human breast cancer cells. J Biol Chem 1994;269:16896–901.PubMedGoogle Scholar
  74. 74.
    Stoica A, Katzenellenbogen BS, Martin MB. Activation of estrogen receptor-α by the heavy metal cadmium. Mol Endocrinol 2000;14:545–3.PubMedGoogle Scholar
  75. 75.
    Martin MB, Voeller HJ, Gelmann Lu EPJ, Stoica EG, Hebert EJ, Reiter R, Singh B, Danielsen M, Pentecost E, Stoica A. Role of cadmium in the regulation of AR gene expression and activity. Endocrinology 2002;143:263–75.PubMedGoogle Scholar
  76. 76.
    Martinez-Campa C, Alonso-Gonzalez CA, Mediavilla MD, Cos S, Gonzalez A, Ramons S, Sanchez-Barcelo EJ. Melatonin inhibits both ERα activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium. J Pineal Res 2006;40:291–96.PubMedGoogle Scholar
  77. 77.
    Beyersmann D, Hechtenberg S. Cadmium, gene regulation, and cellular signaling in mammalian cells. Toxicol Appl Pharmacol 1997;144:247–61.PubMedGoogle Scholar
  78. 78.
    Wilson VS, Bobseine K, Gray LE. Development and characterization of a cell line that stably expresses an estrogen-responsive luciferase reporter for the detection of estrogen receptor agonist and antagonists. Toxicol Sci 2004;81:69–77.PubMedGoogle Scholar
  79. 79.
    Beyersmann D. Effects of carcinogenic metals on gene expression. Toxicol Lett 2002;127:63–8.PubMedGoogle Scholar
  80. 80.
    Ding W, Templeton DM. Activation of parallel mitogen-activated protein kinase cascades and induction of c-fos by cadmium. Toxicol Appl Pharmacol 2000;162:93–9.PubMedGoogle Scholar
  81. 81.
    Silva E, Lopez-Espinosa MJ, Molina-Molina JM, Fernandez M, Olea N, Kortenkamp A. Lack of activity of cadmium in in vitro estrogenicity assays. Toxicol Appl Pharmacol 2006;216:20–8.PubMedGoogle Scholar
  82. 82.
    Pirkle JL, Kaufmann RB, Brody DJ, Hickman T, Gunter EW. Paschal DC. Exposure of the DCUS population to lead, 1991-1994. Environ Health Perspect 1998;106:745–50.PubMedGoogle Scholar
  83. 83.
    Centers for Disease Control (CDC). Death of a child after ingestion of a metallic charm—Minnesota, 2006. MMWR Morb Mortal Wkly Rep 2006;55:340–1.Google Scholar
  84. 84.
    Canfield RL, Henderson CR, Cory-Slechta DA, Cox C, Jusko TA, Lanphear BP. Intellectual impairment in children with blood lead concentrations below 10 μg per deciliter. N Engl J Med 2003;348:1517–26.PubMedGoogle Scholar
  85. 85.
    Selevan SG, Rice DC, Hogan KA, Euling SY, Pfahles-Hutchens A, Bethel J. Blood concentration and delayed puberty in girls. N Engl J Med 2003;348:1527–36.PubMedGoogle Scholar
  86. 86.
    Wu T, Buck GM, Mendola P. Blood lead levels and sexual maturation in U.S. girls: the third Nation Health and Nutrition Examination Survey, 1988-1994. Environ Health Perspect 2003;111:737–41.PubMedGoogle Scholar
  87. 87.
    Denham M, Schell LM, Deane G, Gallo MV, Ravenscroft J, DeCaprio AP, Akwesasne Task Force on the Environment. Relationship of lead, mercury, mirex, dichlorodiphenyldichloroethylene, hexachlorobenzene, and polychlorinated biphenyls to timing of menarche among Akwesasne Mohawk girls. Pediatrics 2005;115:e127–34.PubMedGoogle Scholar
  88. 88.
    Kaplowitz PB, Slora EJ, Wasserman RC, Pedlow SE, Herman-Giddens ME. Earlier onset of puberty in girls: relation to increased body mass index and race. Pediatrics 2001;108:347–53.PubMedGoogle Scholar
  89. 89.
    Schell LM, Gallo MV, Denham M, Ravenscroft J. Effects of pollution on human growth and development: an introduction. J Physiol Anthropol 2006;25:103–2.PubMedGoogle Scholar
  90. 90.
    Ronis MJJ, Badger TM, Shema SJ, Roberson PK, Shaikh F. Effects on pubertal growth and reproduction in rats exposed to lead perinatally or continuously throughout development. J Toxicol Environ Health A 1998;53:327–41.PubMedGoogle Scholar
  91. 91.
    Ronis MJJ, Gandy J, Badger T. Endocrine mechanisms underlying reproductive toxicity in the developing rat chronically exposed to dietary lead. J Toxicol Environ Health A 1998;54:77–99.PubMedGoogle Scholar
  92. 92.
    Dearth RK, Hiney JK, Srivastava V, Burdick SB, Bratton GR, Dees WL. Effects of lead (Pb) exposure during gestation and lactation on female pubertal development in the rat. Reprod Toxicol 2002;16:343–52.PubMedGoogle Scholar
  93. 93.
    McGivern RF, Sokol RZ, Berman NG. Prenatal lead exposure in the rat during the third week of gestation: long-term behavioral, physiological and anatomical effects associated with reproduction. Toxicol Appl Pharmacol 1991;110:206–15.PubMedGoogle Scholar
  94. 94.
    Pine MD, Hiney JK, Dearth RK, Bratton GR, Dees WL. IGF-1 administration to prepubertal female rats can overcome delayed puberty caused by maternal Pb exposure. Reprod Toxicol 2006;21:104–9.PubMedGoogle Scholar
  95. 95.
    Iavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. Effects of low doses of dietary lead on puberty onset in female mice. Reprod Toxicol 2004;19:35–41.PubMedGoogle Scholar
  96. 96.
    Iavicoli I, Carelli G, Stanek EJ, Castellino N, Li Z, Calabrese EJ. Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice. Reprod Toxicol 2006;22:586–90.PubMedGoogle Scholar
  97. 97.
    Parent AS, Teilmann G, Juul A, Skakkebaek NE, Toppari J, Bourguignon JP. The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration. Endocr Rev 2003;24:668–93.PubMedGoogle Scholar
  98. 98.
    Foster WG. Reproductive toxicity of chronic lead exposure in the female cynomolgus monkey. Reprod Toxicol 1992;6:123–31.PubMedGoogle Scholar
  99. 99.
    Wiebe JP, Barr KJ, Buckingham KD. Effect of prenatal and neonatal exposure to lead on gonadotropin receptors and steroidogenesis in rat ovaries. J Toxicol Environ Health 1988;24:461–76.PubMedGoogle Scholar
  100. 100.
    Wide M. Lead exposure on critical days of fetal life affects fertility in the female mouse. Teratology 1985;32:375–80.PubMedGoogle Scholar
  101. 101.
    Junaid M, Chowdhuri DK, Narayan R, Shanker R, Saxena DK. Lead-induced changes in ovarian follicular development and maturation in mice. J Toxicol Environ Health 1997;50:31–40.PubMedGoogle Scholar
  102. 102.
    Taupeau C, Poupon J, Nome F, Lefevre B. Lead accumulation in the mouse ovary after treatment-induced follicular atresia. Reprod Toxicol 2001;15:385–91.PubMedGoogle Scholar
  103. 103.
    Taupeau C, Poupon J, Treton D, Brosse A, Richard Y, Machelon V. Lead reduces messenger RNA and protein levels of cytochrome P450 aromatase and estrogen receptor β in human ovarian granulosa cells. Biol Reprod 2003;68:1982–88.PubMedGoogle Scholar
  104. 104.
    Srivastava V, Dearth RK, Hiney JK, Ramirez LM, Bratton GR, Dees WL. The effects of low-level Pb on steroidogenic acute regulatory protein (StAR) in the prepubertal rat ovary. Toxicol Lett 2004;77:35–40.Google Scholar
  105. 105.
    Benoff S, Jacob A, Hurley IR. Male infertility and environmental exposure to lead and cadmium. Human Reprod Update 2000;6:107–21.Google Scholar
  106. 106.
    Wiebe JP, Salhanick AI, Myer KI. On the mechanism of action of lead in the testis: in vitro suppression of FSH receptors, cyclic AMP and steroidogenesis. Life Sci 1983;32:1997–2005.PubMedGoogle Scholar
  107. 107.
    Rodamilans M, Martinez-Osaba J, To-Figueras J, Rivera-Fillat F, Torra M, Perez P, Corbella J. Inhibition of intratesticular testosterone synthesis by inorganic lead. Toxicol Lett 1988;42:285–90.PubMedGoogle Scholar
  108. 108.
    Thoreux-Manlay A, Le Goascogne C, Segretain D, Jegou B, Pinon-Lataillade P. Lead affects steroidogenesis in rat Leydig cells in vivo and in vitro. Toxicology 1995;103:53–62.PubMedGoogle Scholar
  109. 109.
    Thoreux-Manlay A, Velez de la Calle JF, Olivier MF, Soufir JC, Masse R, Pino-Lataillade G. Impairment of testicular endocrine function after lead intoxication in the adult rat. Toxicology 1995;100:101–9.PubMedGoogle Scholar
  110. 110.
    Liu MY, Leu SF, Yang HY, Huang BM. Inhibitory mechanisms of lead on steroidogenesis in MA-10 mouse Leydig tumor cells. Arch Androl 2003;49:29–38.PubMedGoogle Scholar
  111. 111.
    James WH. Offspring sex ratios at birth as markers of paternal endocrine disruption. Environ Res 2006;100:77–85.PubMedGoogle Scholar
  112. 112.
    Dickinson H, Parker L. Do alcohol and lead change the sex ratio. J Theor Biol 1994;169:313–15.PubMedGoogle Scholar
  113. 113.
    Ansari-Lari M, Saadat M, Hadi N. Influence of GSTT1 null genotype on the offspring sex ratio of gasoline filling station workers. J Epidemiol Commun Health 2004;58:393–4.Google Scholar
  114. 114.
    James WH. Further evidence that mammalian sex ratios at birth are partially controlled by parental hormone levels around the time of conception. Human Reprod 2004;19:1250–56.Google Scholar
  115. 115.
    Simonsen CR, Roge R, Christiansen U, Larsen T, Bonde JP. Effects of paternal blood levels on offspring sex ratio. Reprod Toxicol 2006;22:3–4.PubMedGoogle Scholar
  116. 116.
    Clarkson TW. The three modern faces of mercury. Environ Health Perspect 2002;110(Suppl 1):11–23.PubMedGoogle Scholar
  117. 117.
    Nierenberg DW, Nordgren RE, Chang MB, Siegler RW, Blayney MB, Hochberg F, Toribara TY, Cernichiari E, Clarkson T. Delayed cerebellar disease and death after accidental exposure to dimethylmercury. N Engl J Med 1998;338:1672–6.PubMedGoogle Scholar
  118. 118.
    Mottet NK, Shaw CM, Burbacher TM. Health risks from increases in methylmercury exposure. Environ Health Perspect 1985;63:133–40.PubMedGoogle Scholar
  119. 119.
    Clarkson TW, Magos L, Myers GJ. The toxicology of mercury – current exposures and clinical manifestations. N Engl J Med 2003;349:1731–7.PubMedGoogle Scholar
  120. 120.
    De Rosis F, Anastasio SP, Selvaggi L, Beltrame A, Moriani G. Female reproductive health in two lamp factories: effects of exposure to inorganic mercury vapour and stress factors. Br J Ind Med 1985;42:488–94.PubMedGoogle Scholar
  121. 121.
    Sikorski R, Juszkiewicz T, Paszkowski T, Szprengier-Juszkiewcz T. Women in dental surgeries: reproductive hazards in occupational exposure to metallic mercury. Int Arch Occup Environ Health 1987;59:551–7.PubMedGoogle Scholar
  122. 122.
    Rowland AS, Baird DD, Weinberg CR, Shore DL, Shy CM, Wilcox AJ. The effect of occupational exposure to mercury vapour on the fertility of female dental assistants. Occup Environ Med 1994;51:28–34.PubMedGoogle Scholar
  123. 123.
    Schuurs AHB. Reproductive toxicology of occupational mercury. A review of the literature. J Dent 1999;27:249–56.PubMedGoogle Scholar
  124. 124.
    Lamperti AA, Printz RH. Effects of mercuric chloride on the reproductive cycle of the female hamster. Biol Reprod 1973;8:378–87.PubMedGoogle Scholar
  125. 125.
    Davis BJ, Price HC, O’Connor RW, Fernando R, Rowland AS, Morgan DL. Mercury vapor and female reproductive toxicology. Toxicol Sci 2001;59:291–6.PubMedGoogle Scholar
  126. 126.
    Facemire CF, Gross TS, Guillette LJ Jr. Reproductive impairment in the Florida panther: nature or nurture. Environ Health Perspect 1995;103(Suppl 4):79–86.PubMedGoogle Scholar
  127. 127.
    Mansfield KG, Land ED. Cryptorchidism in Florida panthers: prevalence, features, and influence of genetic restoration. J Wildl Dis 2002;38:693–98.PubMedGoogle Scholar
  128. 128.
    Newman J, Zillioux E, Rich E, Liang L, Newman C. Historical and other patterns of monomethyl and inorganic mercury in the Florida panther (Puma concolor coryi). Arch Environ Contam Toxicol 2004;48:75–80.Google Scholar
  129. 129.
    Vachhrajani KD, Chowdhury AR. Distribution of mercury and evaluation of testicular steroidogenesis in mercuric chloride and methylmercury administered rats. Indian J Exp Biol 1990;28:746–51.PubMedGoogle Scholar
  130. 130.
    Nagar RN, Bhattacharya L. Effect of mercuric chloride on testicular activities in mice, Musculus albinus. J Environ Biol 2001;22:15–8.PubMedGoogle Scholar
  131. 131.
    Ramalingam V, Vimaladevi V, Rajeswary S, Suryavathi V. Effect of mercuric chloride on circulating hormones in adult albino rats. J Environ Biol 2003;24:401–4.PubMedGoogle Scholar
  132. 132.
    Rao MV, Sharma PSN. Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice. Reprod Toxicol 2001;15:705–12.PubMedGoogle Scholar
  133. 133.
    Tong MH, Christenson LK, Song WC. Aberrant cholesterol transport and impaired steroidogenesis in Leydig cells lacking estrogen sulfotransferase. Endocrinology 2004;145:2487–97.PubMedGoogle Scholar
  134. 134.
    Sukocheva OA, Yang Y, Gierthy JF, Seegal RF. Methyl mercury influences growth-related signaling in MCF-7 breast cancer cells. Environ Toxicol 2005;20:32–44.PubMedGoogle Scholar
  135. 135.
    Gierthy JF, Lincoln DW, Roth KE, Bowser SS, Bennett JA, Bradley L, Dickerman HW. Estrogen-stimulation of postconfluent cell accumulation and foci formation of human MCF-7 breast cancer cells. J Cell Biochem 1991;45:177–87.PubMedGoogle Scholar
  136. 136.
    Li X, Zhang S, Safe S. Activation of kinase pathways in MCF-7 cells by 17β-estradiol and structurally diverse estrogenic compounds. J Steroid Biochem Mol Biol 2006;98:122–32.PubMedGoogle Scholar
  137. 137.
    Brugge D, Goble R. The history of uranium mining and the Navajo people. Am J Public Health 2002;92:1410–9.PubMedGoogle Scholar
  138. 138.
    Brugge D, de Lemos JI, Oldmixon B. Exposure pathways and health effects associated with chemical and radiological toxicity of natural uranium: a review. Rev Environ Health 2005;20:177–93.PubMedGoogle Scholar
  139. 139.
    Goldman M, Yaari A, Doshnitzki Z, Cohen-Luria R, Moran A. Nephrotoxicity of uranyl acetate: effect on rat kidney brush border membrane vesicles. Arch Toxicol 2006;80:387–93.PubMedGoogle Scholar
  140. 140.
    Orloff KG, Mistry K, Charp P, Metcalf S, Marino R, Shelly T, Melaro E, Donohoe AM, Jones RL. Human exposure to uranium in groundwater. Environ Res 2004;94:319–26.PubMedGoogle Scholar
  141. 141.
    Maynard E, Dodge H. Studies of the toxicity of various uranium compounds when fed to experimental animals. In: Voeglen C, ed. Pharmacology and Toxicology of Uranium Compounds, New York: McGraw-Hill, 1949:309–76.Google Scholar
  142. 142.
    Arfsten DP, Still KR, Ritchie GD. A review of the effects of uranium and depleted uranium exposure on reproduction and fetal development. Toxicol Ind Health 2001;17:180–91.PubMedGoogle Scholar
  143. 143.
    Domingo JL. Reproductive and developmental toxicity of natural and depleted uranium: a review. Reprod Toxicol 2001;15:603–9.PubMedGoogle Scholar
  144. 144.
    Maconochie N, Doyle P, Carson C. Infertility among male UK veterans of the 1990-1 Gulf war: reproductive cohort study. BMJ 2004;329:196–201.PubMedGoogle Scholar
  145. 145.
    Doyle P, Maconochie N, Davies G, Maconochie I, Pelerin M, Prior S, Lewis S. Miscarriage, stillbirth and congenital malformation in the offspring of UK veterans of the first Gulf war. Int J Epidemiol 2004;33:74–86.PubMedGoogle Scholar
  146. 146.
    McDiarmid MA, Engelhardt S, Oliver M, Guccer P, Wilson PD, Kane R, Kabat M, Kaup B, Anderson L, Hoover D, Brown L, Handwerger B, Albertini RJ, Jacobson-Kram D, Thorne CD, Squibb KS. Health effects of depleted uranium on exposed Gulf war veterans: a 10-year follow-up. J Toxicol Environ Health A 2004;67:277–96.PubMedGoogle Scholar
  147. 147.
    McDiarmid MA, Keogh JP, Hooper FJ, McPhaul K, Squibb K, Kane R, DiPino R, Kabat M, Kaup B, Anderson L, Hoover D, Brown L, Hamilton M, Jacobson-Kram D, Burrows B, Walsh M. Health effects of depleted uranium on exposed Gulf war veterans. Environ Res 2000;82:168–80.PubMedGoogle Scholar
  148. 148.
    McDiarmid MA, Squibb K, Engelhardt S, Oliver M, Gucer P, Wilson PD, Kane R, Kabat M, Kaup B, Anderson L, Hoover D, Brown L, Jacobson-Kram D. Depleted uranium follow-up program. J Occup Environ Med 2001;43:991–1000.PubMedGoogle Scholar
  149. 149.
    Muller C, Ruzicka L, Bakstein J. The sex ratio in the offsprings of uranium miners. Acta Univ Carol Med 1967;13:599–603.Google Scholar
  150. 150.
    Domingo JL, Paternain JL, Llobet JM, Corbella J. The developmental toxicity of uranium in mice. Toxicology 1989;55:143–52.PubMedGoogle Scholar
  151. 151.
    Hindin R, Brugge D, Panikkar B. Teratogenicity of depleted uranium aerosols: a review from an epidemiological perspective. Environ Health 2005;4:17.PubMedGoogle Scholar
  152. 152.
    Shields LM, Wiese WH, Skipper BJ, Charley B, Benally L. Navajo birth outcomes in the Shiprock uranium mining area. Health Phys 1992;63:542–1.PubMedGoogle Scholar
  153. 153.
    Whish SR, Mayer LP, Robinson ZD, Layton TM, Hoyer PB, Dyer CA. Uranium is an estrogen mimic and causes changes in female mouse reproductive tissues. The Endocrine Society 87th Annual Meeting 2005;Abstract P2-261.Google Scholar
  154. 154.
    Getz JE, Sellers M, Whish SR, Dyer CA. Uranium mimics the effects of 17β-estradiol, mediating rapid cell surface morphological changes in MCF-7 human breast cancer cells. Society for the Study of Reproduction 38th Annual Meeting 2005;Abstract 64.Google Scholar
  155. 155.
    Clode SA. Assessment of in vivo assays for endocrine disruption. Best Pract Res Clin Endocrinol Metab 2006;20:35–43.PubMedGoogle Scholar
  156. 156.
    Gordon MN, Osterburg HH, May PC, Finch CE. Effective oral administration of 17β-estradiol to female C57BL/6J mice through the drinking water. Biol Reprod 1986;35:1088–95.PubMedGoogle Scholar
  157. 157.
    Zhang D, Trudeau VL. Integration of membrane and nuclear estrogen receptor signaling. Comp Biochem Physiol A Mol Integr Physiol 2006;144:306–15.PubMedGoogle Scholar
  158. 158.
    Song RX, McPherson RA, Adam L, Bao Y, Shupnik M, Kumar R, Santen RJ. Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation. Mol Endocrinol 2002;16:116–27.PubMedGoogle Scholar
  159. 159.
    Lin RH, Wu LJ, Lee CH, Lin-Shiau SY. Cytogenetic toxicity of uranyl nitrate in Chinese hamster ovary cells. Mutat Res 1993;319:197–203.PubMedGoogle Scholar
  160. 160.
    Stearns DM, Yazzie M, Bradley AS, Coryell VH, Shelley JT, Ashby A, Asplund CS, Lantz RC. Uranyl acetate induces hprt mutations and uranium-DNA adducts in Chinese hamster ovary EM9 cells. Mutagenesis 2005;20:417–23.PubMedGoogle Scholar
  161. 161.
    Tabb MM, Blumberg B. New modes of action for endocrine-disrupting chemicals. Mol Endocrinol 2006;20:475–82.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Cheryl A. Dyer

There are no affiliations available

Personalised recommendations