, Volume 9, Issue 3, pp 206–217 | Cite as

Impact of environmental endocrine disrupting chemicals on the development of obesity

  • Retha R. Newbold


Environmental chemicals with hormone-like activity can disrupt programming of endocrine signaling pathways during development and result in adverse effects, some of which may not be apparent until much later in life. Recent reports link exposure to environmental endocrine disrupting chemicals during development with adverse health consequences, including obesity and diabetes. These particular diseases are quickly becoming significant public health problems and are fast reaching epidemic proportions worldwide. This review summarizes data from experimental animals and humans which support an association of endocrine disrupting chemicals, such as diethylstilbestrol, bisphenol A, phytoestrogens, phthalates, and organotins, with the development of obesity. Potential mechanisms are summarized and future research needs are discussed.

Key words

Bisphenol A Diabetes Endocrine disruptors Metabolic disease Obesogens Phthalates Tributytin Xenoestrogens 


  1. 1.
    Ogden CL, Yanovski SZ, Carroll MD, Flegal KM, 2007 The epidemiology of obesity. Gastroenterology 132: 2087–2102.CrossRefGoogle Scholar
  2. 2.
    Oken E, Gillman MW, 2003 Fetal origins of obesity. Obes Res 11: 496–506.CrossRefGoogle Scholar
  3. 3.
    Cunningham E, 2010 Where can I find obesity statistics? J Am Diet Assoc 110: 656.CrossRefGoogle Scholar
  4. 4.
    Caballero B, 2007 The global epidemic of obesity: an overview. Epidemiol Rev 29: 1–5.CrossRefGoogle Scholar
  5. 5.
    CDC. Report on overweight and obesity, 2008 In: Centers for Disease control and PreventionGoogle Scholar
  6. 6.
    Mcallister EJ, Dhurandhar NV, Keith SW, et al, 2009 Ten putative contributors to the obesity epidemic. Crit Rev Food Sci Nutr 49: 868–913.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Ogden CL, Flegal KM, Carroll MD, Johnson CL, 2002 Prevalence and trends in overweight among US children and adolescents, 1999–2000. JAMA 288: 1728–1732.CrossRefGoogle Scholar
  8. 8.
    Flegal KM, Carroll MD, Ogden CL, Curtin LR, 2010 Prevalence and trends in obesity among US adults, 1999–2008. JAMA 303: 235–241.CrossRefGoogle Scholar
  9. 9.
    Collins S, 2005 Overview of clinical perspectives and mechanisms of obesity. Birth Defects Res A Clin Mol Teratol 73: 470–471.CrossRefGoogle Scholar
  10. 10.
    Mokdad AH, Ford ES, Bowman BA, et al, 2003 Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 289: 76–79.CrossRefGoogle Scholar
  11. 11.
    Mokdad AH, Serdula MK, Dietz WH, Bowman BA, Marks JS, Koplan JP, 1999 The spread of the obesity epidemic in the United States, 1991–1998. JAMA 282: 1519–1522.CrossRefGoogle Scholar
  12. 12.
    Goncharov A, Haase RF, Santiago-Rivera A, et al, 2008 High serum PcBs are associated with elevation of serum lipids and cardiovascular disease in a native american population. Environ Res 106: 226–239.CrossRefGoogle Scholar
  13. 13.
    Gladen BC, Ragan NB, Rogan WJ, 2000 Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. J Pediatr 136: 490–496.CrossRefGoogle Scholar
  14. 14.
    Vasiliu O, Cameron L, Gardiner J, Deguire P, Karmaus W, 2006 Polybrominated biphenyls, polychlorinated biphenyls, body weight, and incidence of adult-onset diabetes mellitus. Epidemiology 17: 352–359.CrossRefGoogle Scholar
  15. 15.
    Lee DH, Lee IK, Jin SH, Steffes M, Jacobs DR, Jr, 2007 Association between serum concentrations of persistent organic pollutants and insulin resistance among nondiabetic adults: results from the national Health and nutrition examination Survey 1999–2002. Diabetes Care 30: 622–628.CrossRefGoogle Scholar
  16. 16.
    Lee DH, Steffes MW, Jacobs DR, Jr, 2008 Can persistent organic pollutants explain the association between serum gamma-glutamyltransferase and type 2 diabetes? Diabetologia 51: 402–407.CrossRefGoogle Scholar
  17. 17.
    Pelletier C, Doucet E, Imbeault P, Tremblay A, 2002 associations between weight loss-induced changes in plasma organochlorine concentrations, serum T(3) concentration, and resting metabolic rate. Toxicol Sci 67: 46–51.CrossRefGoogle Scholar
  18. 18.
    Smink A, Ribas-Fito N, Garcia R, et al, 2008 Exposure to hexachlorobenzene during pregnancy increases the risk of overweight in children aged 6 years. Acta Paediatr 97: 1465–1469.CrossRefGoogle Scholar
  19. 19.
    Stahlhut RW, van Wijngaarden E, Dye TD, Cook S, Swan SH, 2007 Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ Health Perspect 115: 876–882.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Hatch EE, Nelson JW, Qureshi MM, et al, 2008 Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environ Health 7: 27.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Takeuchi T, Tsutsumi O, Ikezuki Y, Takai Y, Taketani Y, 2004 Positive relationship between androgen and the endocrine disruptor, bisphenol a, in normal women and women with ovarian dysfunction. Endocr J 51: 165–169.CrossRefGoogle Scholar
  22. 22.
    Coronado-Gonzalez JA, Del Razo LM, Garcia-Vargas G, Sanmiguel-Salazar F, Escobedo-de La Pena J, 2007 Inorganic arsenic exposure and type 2 diabetes mellitus in Mexico. Environ Res 104: 383–389.CrossRefGoogle Scholar
  23. 23.
    Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E, 2008 Arsenic exposure and prevalence of type 2 diabetes in US adults. JAMA 300: 814–822.CrossRefGoogle Scholar
  24. 24.
    Bern B, 1992 The Fragile Fetus. Princeton, NJ: Princeton Scientific Publishing Co.Google Scholar
  25. 25.
    Heindel JJ, 2007 Role of exposure to environmental chemicals in the developmental basis of disease and dysfunction. Reprod Toxicol 23: 257–259.CrossRefGoogle Scholar
  26. 26.
    Heindel JJ, 2008 Animal models for probing the developmental basis of disease and dysfunction paradigm. Basic Clin Pharmacol Toxicol 102: 76–81.CrossRefGoogle Scholar
  27. 27.
    Heindel JJ, Levin E, 2005 Developmental origins and environmental influences—Introduction. NIEHS symposium. Birth Defects Res A Clin Mol Teratol 73: 469.CrossRefGoogle Scholar
  28. 28.
    Gluckman PD, Hanson MA, 2004 The developmental origins of the metabolic syndrome. Trends endocrinol Metab 15: 183–187.CrossRefGoogle Scholar
  29. 29.
    Colborn T, Dumanoski D, Myers JP, 1996. In our Stolen Future. Penguin Books USA, Inc.Google Scholar
  30. 30.
    NIH, 1999 DES research Update, NIH Publication No. 00-4722, Bethesda, MD.Google Scholar
  31. 31.
    Barker DJ, Eriksson JG, Forsen T, Osmond C, 2002 Fetal origins of adult disease: strength of effects and biological basis. Int J Epidemiol 31: 1235–1239.CrossRefGoogle Scholar
  32. 32.
    vom Saal FS, Akingbemi BT, Belcher SM, et al, 2007 Chapel Hill bisphenol a expert panel consensus statement: integration of mechanisms, effects in animals and potential to impact human health at current levels of exposure. Reprod Toxicol 24: 131–138.CrossRefGoogle Scholar
  33. 33.
    Anway MD, Cupp AS, Uzumcu M, Skinner MK, 2005 Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308: 1466–1469.CrossRefGoogle Scholar
  34. 34.
    Anway MD, Skinner MK, 2008 Epigenetic programming of the germ line: effects of endocrine disruptors on the development of transgenerational disease. Reprod Biomed Online 16: 23–25.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Newbold RR, Padilla-Banks E, Jefferson WN, 2006 Adverse effects of the model environmental estrogen diethylstilbestrol are transmitted to subsequent generations. Endocrinology 147: S11–17.CrossRefGoogle Scholar
  36. 36.
    Skinner MK, Anway MD, 2007 Epigenetic transgen-erational actions of vinclozolin on the development of disease and cancer. Crit Rev Oncog 13: 75–82.CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Skinner MK, Anway MD, Savenkova MI, Gore AC, Crews D, 2008 Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior. PLoS One 3: e3745.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Tang WY, Newbold R, Mardilovich K, et al, 2008 Persistent hy pomethy lation in the promoter of nucleosomal binding protein 1 (Nsbp1) correlates with overexpres-sion of nsbp1 in mouse uteri neonatally exposed to diethylstilbestrol or genistein. Endocrinology 149: 5922–5931.CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Baillie-Hamilton PF, 2002 Chemical toxins: a hypothesis to explain the global obesity epidemic. J Altern Complement Med 8: 185–192.CrossRefGoogle Scholar
  40. 40.
    Heindel JJ, 2003 Endocrine disruptors and the obesity epidemic. Toxicol Sci 76: 247–249.CrossRefGoogle Scholar
  41. 41.
    Newbold RR, Padilla-Banks E, Jefferson WN, Heindel JJ, 2008 Effects of endocrine disruptors on obesity. Int J Androl 31: 201–208.CrossRefGoogle Scholar
  42. 42.
    Newbold RR, Padilla-Banks E, Snyder RJ, Jefferson WN, 2005 Developmental exposure to estrogenic compounds and obesity. Birth Defects Res A Clin Mol Teratol 73: 478–480.CrossRefGoogle Scholar
  43. 43.
    Newbold RR, Padilla-Banks E, Snyder RJ, Jefferson WN, 2007 Perinatal exposure to environmental estrogens and the development of obesity. Mol Nutr Food Res 51: 912–917.CrossRefGoogle Scholar
  44. 44.
    Newbold RR, Padilla-Banks E, Snyder RJ, Phillips TM, Jefferson WN, 2007 Developmental exposure to endocrine disruptors and the obesity epidemic. Reprod Toxicol 23: 290–296.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Grun F, Blumberg B, 2006 Environmental obesogens: organotins and endocrine disruption via nuclear receptor signaling. Endocrinology 147: S50–55.CrossRefGoogle Scholar
  46. 46.
    Grun F, Watanabe H, Zamanian Z, et al, 2006 Endocrine-disrupting organotin compounds are potent inducers of adipogenesis invertebrates. Mol Endocrinol 20: 2141–2155.CrossRefGoogle Scholar
  47. 47.
    Raun A, Preston R. History of diethylstilbestrol use in livestock. 2002.Google Scholar
  48. 48.
    Newbold RR, 1995 Cellular and molecular effects of developmental exposure to diethylstilbestrol: implications for other environmnetal estrogens. Environmental Health Perspectives 103: 83–87.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    McLachlan JA, Newbold RR, Bullock BC, 1980 Long-term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Research 40: 3988–3999.PubMedGoogle Scholar
  50. 50.
    Newbold RR, Bullock BC, McLachlan JA, 1990 Uterine adenocarcinoma in mice following developmental treatment with estrogens: a model for hormonal carcinogenesis. Cancer Research 50: 7677–7681.PubMedGoogle Scholar
  51. 51.
    Newbold R, 2004 Lessons learned from Perinatal exposure to Diethylstilbestrol (DES). Toxicology and Applied Pharmacology 199: 142–150.CrossRefGoogle Scholar
  52. 52.
    Newbold RR, McLachlan JA, 1996 Transplacental hormonal carcinogenesis: diethylstilbestrol as an example. In: Huff J, Boyd J, Barrett JC (eds.), Cellular and Molecular Mechanisms of Hormonal carcinogenesis: Environmental Influences. New York: Wiley-Liss; pp 131–147.Google Scholar
  53. 53.
    Gluckman PD, Hanson MA, Pinal C, 2005 The developmental origins of adult disease. Matern Child Nutr 1: 130–141.CrossRefGoogle Scholar
  54. 54.
    Gillum RF, 1987 The association of the ratio of waist to hip girth with blood pressure, serum cholesterol and serum uric acid in children and youths aged 6–17 years. J Chronic Dis 40: 413–420.CrossRefGoogle Scholar
  55. 55.
    Gesta S, Bluher M, Yamamoto Y, et al, 2006 Evidence for a role of developmental genes in the origin of obesity and body fat distribution. Proc Natl Acad Sci U S A 103: 6676–6681.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Newbold RR, Jefferson WN, Grissom SF, Padilla-Banks E, Snyder RJ, Lobenhofer EK, 2007 Developmental exposure to diethylstilbestrol alters uterine gene expression that may be associated with uterine neoplasia later in life. Mol Carcinog 46: 783–796.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Nikaido Y, Yoshizawa K, Danbara N, et al, 2004 Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring. Reprod Toxicol 18: 803–811.CrossRefGoogle Scholar
  58. 58.
    Zoeller RT, Bansal R, Parris C, 2005 Bisphenol—A, an environmental contaminant that acts as a thyroid hormone receptor antagonist in vitro, increases serum thyroxine, and alters RC3/neurogranin expression in the developing rat brain. Endocrinology 146: 607–612.CrossRefGoogle Scholar
  59. 59.
    Brotons JA, Olea-Serrano MF, Villalobos M, Olea N, 1994 Xenoestrogens released from lacquer coating in food cans. Environmental Health Perspectives 103: 608–612.CrossRefGoogle Scholar
  60. 60.
    Biles JE, McNeal TP, Begley TH, Hollifield HC, 1997 Determination of bisphenol—A in reusable polycarbonate food-contact plastics and migration to food simulating liquids. Journal Agric Food Chem 45: 3541–3544.CrossRefGoogle Scholar
  61. 61.
    Olea N, Pulgar R, Perez P, et al, 1996, Estrogenicity of resin-based composites and sealants used in dentistry. Environ Health Perspect 104: 298–305.CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Calafat AM, Ye X, Wong LY, Reidy JA, Needham LL, 2008 Exposure of the U.S. population to bisphenol a and 4-tertiary-octylphenol: 2003–2004. Environ Health Perspect 116: 39–44.CrossRefGoogle Scholar
  63. 63.
    Takeuchi T, Tsutsumi O, 2002 Serum bisphenol a concentrations showed gender differences, possibly linked to androgen levels. Biochem Biophys Res Commun 291: 76–78.CrossRefGoogle Scholar
  64. 64.
    Ye X, Kuklenyik Z, Needham LL, Calafat AM, 2006 Measuring environmental phenols and chlorinated organic chemicals in breast milk using automated on-line column-switching-high performance liquid chroma-tography-isotope dilution tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 831: 110–115.CrossRefGoogle Scholar
  65. 65.
    Padmanabhan V, Siefert K, Ransom S, et al, 2008 Maternal bisphenol—A levels at delivery: a looming problem? J Perinatol 28: 258–263.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Schonfelder G, Flick B, Mayr E, Talsness C, Paul M, Chahoud I, 2002 In utero exposure to low doses of bisphenol a lead to long-term deleterious effects in the vagina. Neoplasia 4: 98–102.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
    Tetrabromobisphenol A and derivatives: Environmental Health criteria no. 172. In. Geneva: World Health Organization; 1995.Google Scholar
  68. 68.
    European Union Updated European Risk Assessment Report 4,4′-Isopropylidenediphenol (Bisphenol A). Environment Addendum of February 2008 (to be read in conjunction witheU rar of BPa published in 2003). add 325.pdf). In; 2008.Google Scholar
  69. 69.
    Thomsen C, Lundanes E, Becher G, 2002 Brominated flame retardants in archived serum samples from norway: a study on temporal trends and the role of age. Environ Sci Technol 36: 1414–1418.CrossRefGoogle Scholar
  70. 70.
    Wetherill YB, Akingbemi BT, Kanno J, et al, 2007 In vitro molecular mechanisms of bisphenol a action. Reprod Toxicol 24: 178–198.CrossRefGoogle Scholar
  71. 71.
    NTP. CEHR Brief on Bisphenol A. National Toxicology Program, Research Triangle Park, NC. 2008.Google Scholar
  72. 72.
    Richter CA, Birnbaum LS, Farabollini F, et al, 2007 In vivo effects of bisphenol A in laboratory rodent studies. Reprod Toxicol 24: 199–224.CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Howdeshell KL, Hotchkiss AK, Thayer KA, Vandenbergh JG, vom Saal FS, 1999 Exposure to bisphenol A advances puberty. Nature 401: 763–764.CrossRefGoogle Scholar
  74. 74.
    Ashby J, Tinwell H, Haseman J, 1999 Lack of effects for low dose levels of bisphenol a and diethylstilbestrol on the prostate gland of CF1 mice exposed in utero. Regul Toxicol Pharmacol 30: 156–166.CrossRefGoogle Scholar
  75. 75.
    Takai Y, Tsutsumi O, Ikezuki Y, et al, 2001 Preimplantation exposure to bisphenol a advances postnatal development. Reprod Toxicol 15: 71–74.CrossRefGoogle Scholar
  76. 76.
    Honma S, Suzuki A, Buchanan DL, Katsu Y, Watanabe H, Iguchi T, 2002 Low dose effect of in utero exposure to bisphenol A and diethylstilbestrol on female mouse reproduction. Reprod Toxicol 16: 117–122.CrossRefGoogle Scholar
  77. 77.
    Nikaido Y, Danbara N, Tsujita-Kyutoku M, Yuri T, Uehara N, Tsubura A, 2005 Effects of prepubertal exposure to xenoestrogen on development of estrogen target organs in female CD-1 mice. In Vivo 19: 487–494.PubMedGoogle Scholar
  78. 78.
    Rubin BS, Murray MK, Damassa DA, King JC, Soto AM, 2001 Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ Health Perspect 109: 675–680.CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Somm E, Schwitzgebel VM, Toulotte A, et al, 2009 Perinatal exposure to bisphenol a alters early adipogenesis in the rat. Environ Health Perspect 117: 1549–1555.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Sakurai K, Kawazuma M, Adachi T, et al, 2004 Bisphenol a affects glucose transport in mouse 3T3-F442a adipocytes. Br J Pharmacol 141: 209–214.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Masuno H, Kidani T, Sekiya K, et al, 2002 Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. J Lipid Res 43: 676–684.PubMedGoogle Scholar
  82. 82.
    Masuno H, Iwanami J, Kidani T, Sakayama K, Honda K, 2005 Bisphenol a accelerates terminal differentiation of 3T3-l1 cells into adipocytes through the phosphatidyli-nositol 3-kinase pathway. Toxicol Sci 84: 319–327.CrossRefGoogle Scholar
  83. 83.
    Alonso-Magdalena P, Laribi O, Ropero AB, et al, 2005 Low doses of bisphenol a and diethylstilbestrol impair Ca2+ signals in pancreatic alpha-cells through a nonclas-sical membrane estrogen receptor within intact islets of langerhans. Environ Health Perspect 113: 969–977.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Alonso-Magdalena P, Morimoto S, Ripoll C, Fuentes E, Nadal A, 2006 The estrogenic effect of bisphenol a disrupts pancreatic beta-cell function in vivo and induces insulin resistance. Environ Health Perspect 114: 106–112.CrossRefGoogle Scholar
  85. 85.
    Ben-Jonathan N, Hugo ER, Brandebourg TD, 2009 Effects of bisphenol a on adipokine release from human adipose tissue: Implications for the metabolic syndrome. Mol Cell Endocrinol 304: 49–54.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Hugo ER, Brandebourg TD, Woo JG, Loftus J, Alexander JW, Ben-Jonathan N, 2008 Bisphenol A at environmentally relevant doses inhibits adiponectin release from human adipose tissue explants and adipocytes. Environ Health Perspect 116: 1642–1647.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Ropero AB, Alonso-Magdalena P, Garcia-Garcia E, Ripoll C, Fuentes E, Nadal A, 2008 Bisphenol—A disruption of the endocrine pancreas and blood glucose homeostasis. Int J Androl 31: 194–200.CrossRefGoogle Scholar
  88. 88.
    Moutsatsou P, 2007 The spectrum of phytoestrogens in nature: our knowledge is expanding. Hormones (Athens) 6: 173–193.Google Scholar
  89. 89.
    Penza M, Montani C, Romani A, et al, 2006 Genistein affects adipose tissue deposition in a dose-dependent and gender-specific manner. Endocrinology 147: 5740–5751.CrossRefGoogle Scholar
  90. 90.
    Tabb MM, Blumberg B, 2006 New modes of action for endocrine-disrupting chemicals. Mol Endocrinol 20: 475–482.CrossRefGoogle Scholar
  91. 91.
    Melzer D, Rice N, Depledge MH, Henley WE, Galloway TS, 2010 Association between serum perfluoroctanoic acid (PFOA) and Thyroid Disease in the U.S. National Health and Nutrition Examination Survey. Environ Health Perspect 118: 686–692.CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Shinomiya N, Shinomiya M, 2003 Dichlorodiphe-nyltrichloroethane suppresses neurite outgrowth and induces apoptosis in PC 12 pheochromocytoma cells. Toxicol Lett 137: 175–183.CrossRefGoogle Scholar
  93. 93.
    Stettler N, Stallings VA, Troxel AB, et al, 2005 Weight gain in the first week of life and overweight in adulthood: a cohort study of european american subjects fed infant formula. Circulation 111: 1897–1903.CrossRefGoogle Scholar

Copyright information

© Hellenic Endocrine Society 2010

Authors and Affiliations

  1. 1.Developmental Endocrinology and Endocrine Disruptor Section, Laboratory of Molecular Toxicology, and National Toxicology Program, National Institute of Environmental Health Sciences, NIHDHHSResearch Triangle ParkUSA

Personalised recommendations