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  • Review Article
  • Published:

Endocrine disruptors and obesity

Key Points

  • Obesity is an increasing global public health problem

  • Obesity is a disease of the endocrine system, which involves many tissues and metabolic processes

  • The rapid growth of the obesity epidemic over the past few decades suggests that environmental factors might have a role in the aetiology of the disease

  • Obesity probably has its origins during development, when susceptibility to weight gain and alterations in metabolism develop

  • Obesogens are a subclass of endocrine-disrupting chemicals (EDCs) that might predispose individuals to the development of obesity

  • The obesogen hypothesis provides a means for the prevention of obesity by reducing exposure to EDCs during early development

Abstract

The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development. These chemicals, so-called 'obesogens' might predispose some individuals to gain weight despite their efforts to limit caloric intake and increase levels of physical activity. This Review discusses the role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action. The research reviewed here provides knowledge that health scientists can use to inform their research and decision-making processes.

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Figure 1: Potential mechanism by which environmental chemicals cause obesity in animals and in humans.
Figure 2: Potential mechanisms of obesogen action that alter metabolic set-points and increase the risk of obesity.

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References

  1. Hebert, J. R., Allison, D. B., Archer, E., Lavie, C. J. & Blair, S. N. Scientific decision making, policy decisions, and the obesity pandemic. Mayo Clin. Proc. 88, 593–604 (2013).

    Article  PubMed  Google Scholar 

  2. WHO. Global status report on noncommunicable diseases 2010 [online], (2010).

  3. Pulgaron, E. R. & Delamater, A. M. Obesity and type 2 diabetes in children: epidemiology and treatment. Curr. Diab. Rep. 14, 508 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Sturm, R. The effects of obesity, smoking, and drinking on medical problems and costs. Health Aff. (Millwood) 21, 245–253 (2002).

    Article  Google Scholar 

  5. Calkins, K. & Devaskar, S. U. Fetal origins of adult disease. Curr. Probl. Pediatr. Adolesc. Health Care 41, 158–176 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Das, U. N. Obesity: genes, brain, gut, and environment. Nutrition 26, 459–473 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Maric, G. et al. The role of gut hormones in appetite regulation (review). Acta Physiol. Hung. 101, 395–407 (2014).

    Article  CAS  PubMed  Google Scholar 

  8. Exley, M. A., Hand, L., O'Shea, D. & Lynch, L. Interplay between the immune system and adipose tissue in obesity. J. Endocrinol. 223, R41–R48 (2014).

    Article  CAS  PubMed  Google Scholar 

  9. Lanthier, N. & Leclercq, I. A. Adipose tissues as endocrine target organs. Best Pract. Res. Clin. Gastroenterol. 28, 545–558 (2014).

    Article  CAS  PubMed  Google Scholar 

  10. Sohn, J. W. Network of hypothalamic neurons that control appetite. BMB Rep. 48, 229–233 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Barker, D. J., Winter, P. D., Osmond, C., Margetts, B. & Simmonds, S. J. Weight in infancy and death from ischaemic heart disease. Lancet 2, 577–580 (1989).

    Article  CAS  PubMed  Google Scholar 

  12. McAllister, E. J. et al. Ten putative contributors to the obesity epidemic. Crit. Rev. Food Sci. Nutr. 49, 868–913 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Diamanti-Kandarakis, E. et al. Endocrine-disrupting chemicals: an Endocrine Society scientific statement. Endocr. Rev. 30, 293–342 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Casals-Casas, C. & Desvergne, B. Endocrine disruptors: from endocrine to metabolic disruption. Annu. Rev. Physiol. 73, 135–162 (2011).

    Article  CAS  PubMed  Google Scholar 

  15. Baillie-Hamilton, P. F. Chemical toxins: a hypothesis to explain the global obesity epidemic. J. Altern Complement. Med. 8, 185–192 (2002).

    Article  PubMed  Google Scholar 

  16. Zoeller, R. T. et al. Endocrine-disrupting chemicals and public health protection: a statement of principles from The Endocrine Society. Endocrinology 153, 4097–5110 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Regnier, S. M. & Sargis, R. M. Adipocytes under assault: environmental disruption of adipose physiology. Biochim. Biophys. Acta 1842, 520–533 (2014).

    Article  CAS  PubMed  Google Scholar 

  18. Grün, F. & Blumberg, B. Endocrine disrupters as obesogens. Mol. Cell. Endocrinol. 304, 19–29 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Heindel, J. J. et al. Parma consensus statement on metabolic disruptors. Environ. Health 14, 54 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Newbold, R. R. Developmental exposure to endocrine-disrupting chemicals programs for reproductive tract alterations and obesity later in life. Am. J. Clin. Nutr. 94, 1939S–1942S (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Janesick, A. & Blumberg, B. Endocrine disrupting chemicals and the developmental programming of adipogenesis and obesity. Birth Defects Res. C Embryo Today 93, 34–50 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Barouki, R., Gluckman, P. D., Grandjean, P., Hanson, M. & Heindel, J. J. Developmental origins of non-communicable disease: implications for research and public health. Environ. Health 11, 42 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  23. Gluckman, P. D. & Hanson, M. A. Living with the past: evolution, development, and patterns of disease. Science 305, 1733–1736 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Gluckman, P. D., Hanson, M. A., Beedle, A. S. & Raubenheimer, D. Fetal and neonatal pathways to obesity. Front. Horm. Res. 36, 61–72 (2008).

    Article  PubMed  Google Scholar 

  25. Kirchner, S., Kieu, T., Chow, C., Casey, S. & Blumberg, B. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol. Endocrinol. 24, 526–539 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Sumithran, P. et al. Long-term persistence of hormonal adaptations to weight loss. N. Engl. J. Med. 365, 1597–1604 (2011).

    Article  CAS  PubMed  Google Scholar 

  27. Pittenger, M. F. et al. Multilineage potential of adult human mesenchymal stem cells. Science 284, 143–147 (1999).

    Article  CAS  PubMed  Google Scholar 

  28. Vaiserman, A. Early-life exposure to endocrine disrupting chemicals and later-life health outcomes: an epigenetic bridge? Aging Dis. 5, 419–429 (2014).

    PubMed  PubMed Central  Google Scholar 

  29. Adriani, W., Seta, D. D., Dessi-Fulgheri, F., Farabollini, F. & Laviola, G. Altered profiles of spontaneous novelty seeking, impulsive behavior, and response to D-amphetamine in rats perinatally exposed to bisphenol A. Environ. Health Perspect. 111, 395–401 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bernal, A. J. & Jirtle, R. L. Epigenomic disruption: the effects of early developmental exposures. Birth Defects Res. A Clin. Mol. Teratol. 88, 938–944 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Skinner, M. K., Manikkam, M. & Guerrero-Bosagna, C. Epigenetic transgenerational actions of endocrine disruptors. Reprod. Toxicol. 31, 337–343 (2011).

    Article  CAS  PubMed  Google Scholar 

  32. Desai, M., Jellyman, J. K. & Ross, M. G. Epigenomics, gestational programming and risk of metabolic syndrome. Int. J. Obes. (Lond.) 39, 633–641 (2015).

    Article  CAS  Google Scholar 

  33. Murphy, S. K. & Jirtle, R. L. Imprinting evolution and the price of silence. Bioessays 25, 577–588 (2003).

    Article  CAS  PubMed  Google Scholar 

  34. Colaneri, A. et al. A minimal set of tissue-specific hypomethylated CpGs constitute epigenetic signatures of developmental programming. PLoS ONE 8, e72670 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Remely, M., de la Garza, A. L., Magnet, U., Aumueller, E. & Haslberger, A. G. Obesity: epigenetic regulation—recent observations. Biomol. Concepts 6, 163–175 (2015).

    Article  CAS  PubMed  Google Scholar 

  36. Waterland, R. A. Epigenetic mechanisms affecting regulation of energy balance: many questions, few answers. Annu. Rev. Nutr. 34, 337–355 (2014).

    Article  CAS  PubMed  Google Scholar 

  37. Grun, F. et al. Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Mol. Endocrinol. 20, 2141–2155 (2006).

    Article  CAS  PubMed  Google Scholar 

  38. Lane, R. H. Fetal programming, epigenetics, and adult onset disease. Clin. Perinatol. 41, 815–831 (2014).

    Article  PubMed  Google Scholar 

  39. McGowan, P. O. & Roth, T. L. Epigenetic pathways through which experiences become linked with biology. Dev. Psychopathol. 27, 637–648 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Chamorro-Garcia, R. & Blumberg, B. Transgenerational effects of obesogens and the obesity epidemic. Curr. Opin. Pharmacol. 19, 153–158 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Thayer, K. A., Heindel, J. J., Bucher, J. R. & Gallo, M. A. Role of environmental chemicals in diabetes and obesity: a National Toxicology Program workshop review. Environ. Health Perspect. 120, 779–789 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kupfer, D. J., Coble, P. A. & Rubinstein, D. Changes in weight during treatment for depression. Psychosom. Med. 41, 535–544 (1979).

    Article  CAS  PubMed  Google Scholar 

  43. Shim, W. S. et al. The long-term effects of rosiglitazone on serum lipid concentrations and body weight. Clin. Endocrinol. (Oxf.) 65, 453–459 (2006).

    Article  CAS  Google Scholar 

  44. Serretti, A. & Mandelli, L. Antidepressants and body weight: a comprehensive review and meta-analysis. J. Clin. Psychiatry 71, 1259–1272 (2010).

    Article  PubMed  Google Scholar 

  45. Chamorro-Garcia, R. et al. Transgenerational inheritance of prenatal obesogen exposure Environ. Health Perspect. 121, 359–366 (2012).

    Article  CAS  Google Scholar 

  46. Oken, E., Levitan, E. B. & Gillman, M. W. Maternal smoking during pregnancy and child overweight: systematic review and meta-analysis. Int. J. Obes. (Lond.) 32, 201–210 (2008).

    Article  CAS  Google Scholar 

  47. Ino, T. Maternal smoking during pregnancy and offspring obesity: meta-analysis. Pediatr. Int. 52, 94–99 (2010).

    Article  PubMed  Google Scholar 

  48. Irigaray, P. et al. Benzo[a]pyrene impairs β-adrenergic stimulation of adipose tissue lipolysis and causes weight gain in mice. A novel molecular mechanism of toxicity for a common food pollutant. FEBS J. 273, 1362–1372 (2006).

    Article  CAS  PubMed  Google Scholar 

  49. Backes, C. H., Nelin, T., Gorr, M. W. & Wold, L. E. Early life exposure to air pollution: how bad is it? Toxicol. Lett. 216, 47–53 (2013).

    Article  CAS  PubMed  Google Scholar 

  50. Vadillo-Ortega, F. et al. Air pollution, inflammation and preterm birth: a potential mechanistic link. Med. Hypotheses 82, 219–224 (2014).

    Article  CAS  PubMed  Google Scholar 

  51. Rundle, A. et al. Association of childhood obesity with maternal exposure to ambient air polycyclic aromatic hydrocarbons during pregnancy. Am. J. Epidemiol. 175, 1163–1172 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  52. McConnell, R. et al. Does near-roadway air pollution contribute to childhood obesity? Pediatr. Obes. http://dx.doi.org/10.1111/ijpo.12016 (2015).

  53. Jerrett, M. et al. Traffic-related air pollution and obesity formation in children: a longitudinal, multilevel analysis. Environ. Health 13, 49 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Bolton, J. L. et al. Prenatal air pollution exposure induces neuroinflammation and predisposes offspring to weight gain in adulthood in a sex-specific manner. FASEB J. 26, 4743–4754 (2012).

    Article  CAS  PubMed  Google Scholar 

  55. Zheng, Z. et al. Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model. J. Hepatol. 58, 148–154 (2013).

    Article  CAS  PubMed  Google Scholar 

  56. Sun, Q. et al. Ambient air pollution exaggerates adipose inflammation and insulin resistance in a mouse model of diet-induced obesity. Circulation 119, 538–546 (2009).

    Article  CAS  PubMed  Google Scholar 

  57. Kannan, K., Senthilkumar, K. & Giesy, J. P. Occurrence of butyltin compounds in human blood. Environ. Sci. Technol. 33, 1776–1779 (1999).

    Article  CAS  Google Scholar 

  58. Kanayama, T., Kobayashi, N., Mamiya, S., Nakanishi, T. & Nishikawa, J. Organotin compounds promote adipocyte differentiation as agonists of the peroxisome proliferator-activated receptor γ/retinoid X receptor pathway. Mol. Pharmacol. 67, 766–774 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Pereira-Fernandes, A. et al. Toxicogenomics in the 3T3-L1 cell line, a new approach for screening of obesogenic compounds. Toxicol. Sci. 140, 352–363 (2014).

    Article  CAS  PubMed  Google Scholar 

  60. Inadera, H. Developmental origins of obesity and type 2 diabetes: molecular aspects and role of chemicals. Environ. Health Prev. Med. 18, 185–197 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Watt, J. & Schlezinger, J. J. Structurally-diverse, PPARγ-activating environmental toxicants induce adipogenesis and suppress osteogenesis in bone marrow mesenchymal stromal cells. Toxicology 331, 66–77 (2015).

    Article  CAS  PubMed  Google Scholar 

  62. Blumberg, B. Obesogens, stem cells and the maternal programming of obesity. J. Dev. Orig. Health Dis. 2, 3–8 (2011).

    Article  CAS  PubMed  Google Scholar 

  63. Kirchner, S., Kieu, T., Chow, C., Casey, S. & Blumberg, B. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol. Endocrinol. 24, 526–539 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Grun, F. & Blumberg, B. Environmental obesogens: organotins and endocrine disruption via nuclear receptor signalling. Endocrinology 147, S50–S55 (2006).

    Article  CAS  PubMed  Google Scholar 

  65. Chamorro-Garcia, R. et al. Transgenerational inheritance of increased fat depot size, stem cell reprogramming, and hepatic steatosis elicited by prenatal exposure to the obesogen tributyltin in mice. Environ. Health Perspect. 121, 359–366 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Zuo, Z. et al. Tributyltin causes obesity and hepatic steatosis in male mice. Environ. Toxicol. 26, 79–85 (2011).

    Article  CAS  PubMed  Google Scholar 

  67. Vandenberg, L. N., Maffini, M. V., Sonnenschein, C., Rubin, B. S. & Soto, A. M. Bisphenol-A and the great divide: a review of controversies in the field of endocrine disruption. Endocr. Rev. 30, 75–95 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Oppeneer, S. J. & Robien, K. Bisphenol A exposure and associations with obesity among adults: a critical review. Public Health Nutr. 18, 1847–1863 (2015).

    Article  PubMed  Google Scholar 

  69. Le Corre, L., Besnard, P. & Chagnon, M. C. BPA, an energy balance disruptor. Crit. Rev. Food Sci. Nutr. 55, 769–777 (2015).

    Article  CAS  PubMed  Google Scholar 

  70. Mirmira, P. & Evans-Molina, C. Bisphenol A, obesity, and type 2 diabetes mellitus: genuine concern or unnecessary preoccupation? Transl Res. 164, 13–21 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Lakind, J. S., Goodman, M. & Mattison, D. R. Bisphenol A and indicators of obesity, glucose metabolism/type 2 diabetes and cardiovascular disease: a systematic review of epidemiologic research. Crit. Rev. Toxicol. 44, 121–150 (2014).

    Article  CAS  PubMed  Google Scholar 

  72. Li, D. K. et al. Urine bisphenol-A level in relation to obesity and overweight in school-age children. PLoS ONE 8, 1–6 (2013).

    Google Scholar 

  73. Trasande, L., Attina, T. M. & Blustein, J. Association between urinary bisphenol A concentration and obesity prevalence in children and adolescents. JAMA 308, 1113–1121 (2012).

    Article  CAS  PubMed  Google Scholar 

  74. Harley, K. G. et al. Prenatal and early childhood bisphenol A concentrations and behavior in school-aged children. Environ. Res. 126, 43–50 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Troisi, J. et al. Placental concentrations of bisphenol A and birth weight from births in the Southeastern U.S. Placenta 35, 947–952 (2014).

    Article  CAS  PubMed  Google Scholar 

  76. Miao, M., Yuan, W., Zhu, G., He, X. & Li, D. K. In utero exposure to bisphenol-A and its effect on birth weight of offspring. Reprod. Toxicol. 32, 64–68 (2011).

    Article  CAS  PubMed  Google Scholar 

  77. Braun, J. M. et al. Variability and predictors of urinary bisphenol A concentrations during pregnancy. Environ. Health Perspect. 119, 131–137 (2010).

    Article  CAS  PubMed Central  Google Scholar 

  78. Masuno, H. et al. Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. J. Lipid Res. 43, 676–684 (2002).

    CAS  PubMed  Google Scholar 

  79. Sakurai, K. et al. Bisphenol A affects glucose transport in mouse 3T3-F442A adipocytes. Br. J. Pharmacol. 141, 209–214 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Angle, B. M. et al. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reprod. Toxicol. 42, 256–268 (2013).

    Article  CAS  PubMed  Google Scholar 

  81. Mackay, H. et al. Organizational effects of perinatal exposure to bisphenol-A and diethylstilbestrol on arcuate nucleus circuitry controlling food intake and energy expenditure in male and female CD-1 mice. Endocrinology 154, 1465–1475 (2013).

    Article  CAS  PubMed  Google Scholar 

  82. Olea, N. et al. Estrogenicity of resin-based composites and sealants used in dentistry. Environ. Health Perspect. 104, 298–305 (1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Rubin, B. S. Bisphenol A: an endocrine disruptor with widespread exposure and multiple effects. J. Steroid Biochem. Mol. Biol. 127, 27–34 (2011).

    Article  CAS  PubMed  Google Scholar 

  84. Masuno, H., Iwanami, J., Kidani, T., Sakayama, K. & Honda, K. Bisphenol A accelerates terminal differentiation of 3T3-L1 cells into adipocytes through the phosphatidylinositol 3-kinase pathway. Toxicol. Sci. 84, 319–327 (2005).

    Article  CAS  PubMed  Google Scholar 

  85. Chamorro-Garcia, R. et al. Bisphenol A diglycidyl ether induces adipogenic differentiation of multipotent stromal stem cells through a peroxisome proliferator-activated receptor γ-independent mechanism. Environ. Health Perspect. 120, 984–989 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Ross, M. G. & Desai, M. Developmental programming of offspring obesity, adipogenesis, and appetite. Clin. Obstet. Gynecol. 56, 529–536 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Anderson, O. S. et al. Perinatal bisphenol A exposure promotes hyperactivity, lean body composition, and hormonal responses across the murine life course. FASEB J. 27, 1784–1792 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Kendig, E. L. et al. Estrogen-like disruptive effects of dietary exposure to bisphenol A or 17α-ethinyl estradiol in CD1 mice. Int. J. Toxicol. 31, 537–550 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Mirmira, P. & Evans-Molina, C. Bisphenol A, obesity, and type 2 diabetes mellitus: genuine concern or unnecessary preoccupation? Transl Res. 164, 13–21 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Boucher, J. G., Boudreau, A., Ahmed, S. & Atlas, E. Effects of bisphenol A β-D-glucuronide (BPA-G) on adipogenesis in human and murine preadipocytes. Environ. Health Perspect. http://dx.doi.org/10.1289/ehp.1409143 (2015).

  91. Trasande, L. Further limiting bisphenol A in food uses could provide health and economic benefits. Health Aff. (Millwood) 33, 316–323 (2014).

    Article  Google Scholar 

  92. Legler, J. et al. Obesity, diabetes, and associated costs of exposure to endocrine-disrupting chemicals in the European Union. J. Clin. Endocrinol. Metab. 100, 1278–1288 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Intergovernmental Panel on Climate Change. Fifth assessment report (AR5) [online], (2015).

  94. Stapleton, H. M., Eagle, S., Sjodin, A. & Webster, T. F. Serum PBDEs in a North Carolina toddler cohort: associations with handwipes, house dust, and socioeconomic variables. Environ. Health Perspect. 120, 1049–1054 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Schecter, A., Papke, O., Joseph, J. E. & Tung, K. C. Polybrominated diphenyl ethers (PBDEs) in U.S. computers and domestic carpet vacuuming: possible sources of human exposure. J. Toxicol. Environ. Health A 68, 501–513 (2005).

    Article  CAS  PubMed  Google Scholar 

  96. Hallgren, S., Sinjari, T., Hakansson, H. & Darnerud, P. O. Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice. Arch. Toxicol. 75, 200–208 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Hoppe, A. A. & Carey, G. B. Polybrominated diphenyl ethers as endocrine disruptors of adipocyte metabolism. Obesity (Silver Spring) 15, 2942–2950 (2007).

    Article  CAS  Google Scholar 

  98. van der Ven, L. T. et al. A 28-day oral dose toxicity study enhanced to detect endocrine effects of hexabromocyclododecane in Wistar rats. Toxicol. Sci. 94, 281–292 (2006).

    Article  CAS  PubMed  Google Scholar 

  99. van der Ven, L. T. et al. A 28-day oral dose toxicity study enhanced to detect endocrine effects of a purified technical pentabromodiphenyl ether (pentaBDE) mixture in Wistar rats. Toxicology 245, 109–122 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Chao, H. R., Wang, S. L., Lee, W. J., Wang, Y. F. & Papke, O. Levels of polybrominated diphenyl ethers (PBDEs) in breast milk from central Taiwan and their relation to infant birth outcome and maternal menstruation effects. Environ. Int. 33, 239–245 (2007).

    Article  CAS  PubMed  Google Scholar 

  101. Herbstman, J. B. et al. Birth delivery mode modifies the associations between prenatal polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) and neonatal thyroid hormone levels. Environ. Health Perspect. 116, 1376–1382 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Legler, J. et al. The OBELIX project: early life exposure to endocrine disruptors and obesity. Am. J. Clin. Nutr. 94, 1933S–1938S (2011).

    Article  CAS  PubMed  Google Scholar 

  103. Erkin-Cakmak, A. et al . In utero and childhood polybrominated diphenyl ether exposures and body mass at age 7 years: the CHAMACOS study. Environ. Health Perspect. 123, 636–642 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Bastos Sales, L. et al. Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation. Toxicol. In Vitro 27, 1634–1643 (2013).

    Article  CAS  PubMed  Google Scholar 

  105. Suvorov, A., Battista, M. C. & Takser, L. Perinatal exposure to low-dose 2,2′,4,4′-tetrabromodiphenyl ether affects growth in rat offspring: what is the role of IGF-1? Toxicology. 260, 126–131 (2009).

    Article  CAS  PubMed  Google Scholar 

  106. Patisaul, H. B. et al. Accumulation and endocrine disrupting effects of the flame retardant mixture Firemaster® 550 in rats: an exploratory assessment. J. Biochem. Mol. Toxicol. 27, 124–136 (2013).

    Article  CAS  PubMed  Google Scholar 

  107. Belcher, S. M., Cookman, C. J., Patisaul, H. B. & Stapleton, H. M. In vitro assessment of human nuclear hormone receptor activity and cytotoxicity of the flame retardant mixture FM 550 and its triarylphosphate and brominated components. Toxicol. Lett. 228, 93–102 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Pillai, H. K. et al. Ligand binding and activation of PPARγ by Firemaster® 550: effects on adipogenesis and osteogenesis in vitro. Environ. Health Perspect. 122, 1225–1232 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Bourez, S. et al. The dynamics of accumulation of PCBs in cultured adipocytes vary with the cell lipid content and the lipophilicity of the congener. Toxicol. Lett. 216, 40–46 (2013).

    Article  CAS  PubMed  Google Scholar 

  110. Elobeid, M. A., Brock, D. W., Allison, D. B., Padilla, M. A. & Ruden, D. M. Endocrine disruptors and obesity: an examination of selected persistent organic pollutants in the NHANES 1999–2002 data. Int. J. Environ. Res. Public Health 7, 2988–3005 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Cupul-Uicab, L. A., Klebanoff, M. A., Brock, J. W. & Longnecker, M. P. Prenatal exposure to persistent organochlorines and childhood obesity in the U.S. Collaborative Perinatal Project. Environ. Health Perspect. 121, 1103–1109 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Tang-Peronard, J. L. et al. Association between prenatal polychlorinated biphenyl exposure and obesity development at ages 5 and 7 y: a prospective cohort study of 656 children from the Faroe Islands. Am. J. Clin. Nutr. 99, 5–13 (2014).

    Article  CAS  PubMed  Google Scholar 

  113. Heudorf, U., Mersch-Sundermann, V. & Angerer, J. Phthalates: toxicology and exposure. Int. J. Hyg. Environ. Health 210, 623–634 (2007).

    Article  CAS  PubMed  Google Scholar 

  114. Hannon, P. R. & Flaws, J. A. The effects of phthalates on the ovary. Front. Endocrinol. 6, 8 (2015).

    Article  Google Scholar 

  115. Cai, H. et al. Human urinary/seminal phthalates or their metabolite levels and semen quality: a meta-analysis. Environ. Res. 142, 486–494 (2015).

    Article  CAS  PubMed  Google Scholar 

  116. Hao, C., Cheng, X., Guo, J., Xia, H. & Ma, X. Perinatal exposure to diethyl-hexyl-phthalate induces obesity in mice. Front. Biosci. (Elite Ed.) 5, 725–733 (2013).

    Article  Google Scholar 

  117. Hao, C., Cheng, X., Xia, H. & Ma, X. The endocrine disruptor mono-(2-ethylhexyl) phthalate promotes adipocyte differentiation and induces obesity in mice. Biosci. Rep. 32, 619–629 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Schmidt, J. S., Schaedlich, K., Fiandanese, N., Pocar, P. & Fischer, B. Effects of di(2-ethylhexyl) phthalate (DEHP) on female fertility and adipogenesis in C3H/N. mice. Environ. Health Perspect. 120, 1123–1129 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Biemann, R., Fischer, B. & Navarrete Santos, A. Adipogenic effects of a combination of the endocrine-disrupting compounds bisphenol A, diethylhexylphthalate, and tributyltin. Obes. Facts 7, 48–56 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Feige, J. N. et al. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor γ modulator that promotes adipogenesis. J. Biol. Chem. 282, 19152–19166 (2007).

    Article  CAS  PubMed  Google Scholar 

  121. Hurst, C. H. & Waxman, D. J. Activation of PPARα and PPARγ by environmental phthalate monoesters. Toxicol. Sci. 74, 297–308 (2003).

    Article  CAS  PubMed  Google Scholar 

  122. Biemann, R. et al. Endocrine disrupting chemicals affect the adipogenic differentiation of mesenchymal stem cells in distinct ontogenetic windows. Biochem. Biophys. Res. Commun. 417, 747–52 (2012).

    Article  CAS  PubMed  Google Scholar 

  123. Ferguson, K. K., O'Neill, M. S. & Meeker, J. D. Environmental contaminant exposures and preterm birth: a comprehensive review. J. Toxicol. Environ. Health Part B Crit. Rev. 16, 69–113 (2013).

    Article  CAS  Google Scholar 

  124. Barry, V., Darrow, L. A., Klein, M., Winquist, A. & Steenland, K. Early life perfluorooctanoic acid (PFOA) exposure and overweight and obesity risk in adulthood in a community with elevated exposure. Environ. Res. 132, 62–69 (2014).

    Article  CAS  PubMed  Google Scholar 

  125. Halldorsson, T. I. et al. Prenatal exposure to perfluorooctanoate and risk of overweight at 20 years of age: a prospective cohort study. Environ. Health Perspect. 120, 668–673 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Hines, E. P. et al. Phenotypic dichotomy following developmental exposure to perfluorooctanoic acid (PFOA) in female CD-1 mice: Low doses induce elevated serum leptin and insulin, and overweight in mid-life. Mol. Cell. Endocrinol. 304, 97–105 (2009).

    Article  CAS  PubMed  Google Scholar 

  127. Ngo, H. T., Hetland, R. B., Sabaredzovic, A., Haug, L. S. & Steffensen, I. L. In utero exposure to perfluorooctanoate (PFOA) or perfluorooctane sulfonate (PFOS) did not increase body weight or intestinal tumorigenesis in multiple intestinal neoplasia (Min/+) mice. Environ. Res. 132, 251–263 (2014).

    Article  CAS  PubMed  Google Scholar 

  128. Guerrero-Bosagna, C. & Skinner, M. K. Environmentally induced epigenetic transgenerational inheritance of phenotype and disease. Mol. Cell. Endocrinol. 354, 3–8 (2012).

    Article  CAS  PubMed  Google Scholar 

  129. Anway, M. D. & Skinner, M. K. Epigenetic transgenerational actions of endocrine disruptors. Endocrinology 147, S43–S49 (2006).

    Article  CAS  PubMed  Google Scholar 

  130. Nilsson, E. et al. Environmentally induced epigenetic transgenerational inheritance of ovarian disease. PLoS ONE 7, e36129 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Wolstenholme, J. T. et al. Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression. Endocrinology 153, 3828–3838 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Skinner, M. K. et al. Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. BMC Med. 11, 228 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Tracey, R., Manikkam, M., Guerrero-Bosagna, C. & Skinner, M. K. Hydrocarbons (jet fuel JP-8) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. Reprod. Toxicol. 36, 104–116 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. Manikkam, M., Tracey, R., Guerrero-Bosagna, C. & Skinner, M. K. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS ONE 8, e55387 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Manikkam, M., Tracey, R., Guerrero-Bosagna, C. & Skinner, M. K. Pesticide and insect repellent mixture (permethrin and DEET) induces epigenetic transgenerational inheritance of disease and sperm epimutations. Reprod. Toxicol. 34, 708–719 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Vickers, M. H. Early life nutrition, epigenetics and programming of later life disease. Nutrients 6, 2165–2178 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Aiken, C. E. & Ozanne, S. E. Transgenerational developmental programming. Hum. Reprod. Update 20, 63–75 (2014).

    Article  PubMed  Google Scholar 

  138. Heard, E. & Martienssen, R. A. Transgenerational epigenetic inheritance: myths and mechanisms. Cell 157, 95–109 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Tang, W. W. et al. A unique gene regulatory network resets the human germline epigenome for development. Cell 161, 1453–1467 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Daxinger, L. & Whitelaw, E. Transgenerational epigenetic inheritance: more questions than answers. Genome Res. 20, 1623–1628 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Heindel, J. J. & Schug, T. T. The perfect storm for obesity. Obesity (Silver Spring) 21, 1079–1080 (2013).

    Article  Google Scholar 

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J.J.H., R.N. and T.T.S. researched data for the article, provided substantial contributions to discussions of content, wrote the article and reviewed and/or edited the manuscript before submission.

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Heindel, J., Newbold, R. & Schug, T. Endocrine disruptors and obesity. Nat Rev Endocrinol 11, 653–661 (2015). https://doi.org/10.1038/nrendo.2015.163

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