Environmental Pollutants-Endocrine Disturbers: Effects on Health and Nutrition from an Epigenetic Perspective

Abstract

Endocrine-disrupting chemicals (EDCs), commonly referred to environmental pollutants, have been reported to adversely affect health through epigenetic mechanisms. EDCs are classified in various ways and are extensively used in cosmetics, industry, and agriculture. They can be found in drinking water, soil, and the air we breathe. EDCs can directly or indirectly cause epigenetic changes, which include DNA-level alterations, chromatin-level modifications and post-transcriptional epigenetic mechanisms. The interaction between environmental pollutants and nutrition is bidirectional. Epigenetic changes resulting from malnutrition and and exposure to environmental pollutants exhibit similarities. Diets high in energy density but low in essential nutrients may exacerbate exposure to environmental contaminants and negatively impact overall nutritional status. Conversely, a diet rich in bioactive nutrients, such as polyphenols and anti-inflammatory fatty acids, has the potential to mitigate the inflammatory and oxidative effects associated with pollutant exposure. This narrative review discusses the impact of endocrine- disrupting chemicals, also known as environmental pollutants, on human health and nutrition through various epigenetic mechanisms.

Keywords

• endocrine disruptor
• epigenetics
• nutrition
• health
• environmental pollutants

Çevresel Kirleticiler-Endokrin Bozucular: Epigenetik Bakış Açısıyla Sağlık ve Beslenmeye Etkileri

Abstract

Çevresel kirleticiler olarak da bilinen endokrin bozucu kimyasalların epigenetik mekanizmalar üzerinden sağlığı olumsuz etkilediği belirtilmektedir. Endokrin bozucu kimyasallar farklı şekillerde sınıflandırılmakta olup kozmetik, endüstri ve tarımda yaygın olarak kullanılmaktadır. Bu maddelere içme sularından, topraktan ve solunan havadan bulaş olabilmektedir. Endokrin bozucu kimyasallar doğrudan veya dolaylı olarak epigenetik değişikliklere neden olur. DNA düzeyindeki modifikasyonlar, kromatin düzeyindeki modifikasyonlar ve posttranskripsiyonel epigenetik mekanizmalar arasında yer alır. Çevresel kirleticilerle beslenme etkileşimi iki yönlü olmaktadır. Yetersiz beslenme ve çevresel kirleticilerin neden olduğu epigenetik değişiklikler benzerdir. Yüksek enerji yoğunluğu ve düşük besin öğesi profiline sahip besinlerin çevresel kirletici maruziyetini şiddetlendirebileceği ve genel beslenme durumunu etkileyebileceği belirtilmektedir. Polifenoller ve antiinflamatuar yağ asitleri gibi biyoaktif besin bileşenlerini içeren besinlerden zengin bir diyet ise, kirletici maruziyetinin inflamatuar ve oksidatif özelliklerini azaltma kapasitesine sahiptir. Bu geleneksel derlemede, çevresel kirletici olarak da bilinen endokrin bozucu kimyasal maddelerin farklı epigenetik mekanizmalar aracılığı ile insan sağlığı ve beslenmesi üzerine etkilerinden bahsedilmiştir.

Keywords

• endokrin bozucu
• epigenetik
• beslenme
• sağlık
• çevresel kirleticiler

References

1. Ayissi VB, Ebrahimi A, Schluesenner H. Epigenetic effects of natural polyphenols: a focus on SIRT1-mediated mechanisms. Molecular Nutrition & Food Research. 2014;58(1):22–32. DOI: 10.1002/ mnfr.201300195.
2. Ross SA, Davis CD. The emerging role of microRNAs and nutrition in modulating health and disease. Annual Review of Nutrition. 2014;34:305–36. DOI: 10.1146/annurev-nutr-071813-105729.
3. World Health Organization (WHO)/Uluslararası Kimyasal Güvenlik Programı (IPCS). International program on chemical safety. global assessment of endocrine disrupting chemicals. 2016. Available from: http://www.who.int/ipcs/en/.
4. US Environmental Protection Agency (EPA). Research on endocrine disruptors. 2016. Available from: https://www.epa.gov/chemical- research/research- endocrine-disruptors.
5. Diamanti-Kandarakis E, Bourguignon JP, Giudice LC, Hauser R. Endocrine-disrupting chemicals: an endocrine society scientific statement. Endocrine Reviews. 2009;30(4):293– 342. DOI: org/10.1210/ er.2009-0002.
6. Caliman FA, Gavrilescu M. Pharmaceuticals, personal care products and endocrine disrupting agents in the environment – a review. Clean – Soil Air Water. 2019;37(4–5):277–303. DOI: 10.1002/clen.200900038.
7. Maqbool F, Mostafalou S, Bahadar H, Abdollahi M. Review of endocrine disorders associated with environmental toxicants and possible involved mechanism. Life Sciences. 2015;145:265-73. DOI: 10.1016/j.lfs.2015.10.022.
8. Gore AC, Crews D, Doan LL, La Merrill M, Patisaul H, Zota A. Introduction to endocrine disrupting chemicals (EDCS) – a guide for public interest organizations and policy-makers. Endocrine Society and IPEN. 2014;1-76.

9. Lee MM. Endocrine disrupters. A Current Review of Pediatric Endocrinology. 2007;109-18.
10. Kabir ER, Rahman MS, Rahman IA. Review on endocrine disruptors and their possible impacts on human health. Enviromental Toxicology and Pharmacology. 2015;40(1):241-58. DOI: 10.1016/j.etap.2015.06.009.
11. Dodson RE, Nishioka M, Standley LJ, Perovich LJ, Brody JG, Rudel RA. Endocrine disruptors and asthma-associated chemicals in consumer products. Environmental Health Perspectives. 2012;120(7):935–43. DOI: 10.1289/ehp.1104052.
12. Wuttke W, Jarry H, Seidlovα-Wuttke D. Definition, classification and mechanism of action of endocrine disrupting chemicals. Hormones. 2010;9(1):9-15. DOI: 10.1007/BF03401276.
13. Stumm-Zollinger E, Fair GM. Biodegradation of steroid hormones. Journal - Water Pollution Control Federation. 1965;37(11):1506–10.
14. Dolinoy DC, Jirtle RL. Environmental epigenomics in human health and disease. Environmental and Molecular Mutagenesis. 2008;49(1):4–8. DOI: 10.1002/em.20366.
15. Anway MD, Rekow SS, Skinner MK. Transgenerational epigenetic programming of the embryonic testis transcriptome. Genomics. 2008;91(1):30–40. DOI: 10.1016/j.ygeno.2007.10.002.
16. Perera F, Herbstman J. Prenatal environmental exposures, epigenetics, and disease. Reproductive Toxicology. 2011;31(3):363–73. DOI: 10.1016/j.reprotox.2010.12.055.
17. Kahn LG, Philippat C, Nakayama SF, Slama R, Trasande L. Endocrine- disrupting chemicals: implications for human health. The Lancet Diabetes & Endocrinology. 2020;8(8):703-18. DOI: 10.1016/S2213- 8587(20)30129-7.
18. Choudhuri S, Cui Y, Klaassen CD. Molecular targets of epigenetic regulation and effectors of environmental influences. Toxicology and Applied Pharmacology. 2010;245(3):378–93. DOI: 10.1016/j. taap.2010.03.022.
19. Kundakovic M, Champagne FA. Epigenetic perspective on the developmental effects of bisphenol A. Brain, Behavior, and Immunity. 2011;25(6):1084–93. DOI: 10.1016/j.bbi.2011.02.005.
20. Reddy JK, Rao MS. Oxidative DNA damage caused by persistent peroxisome proliferation: its role in hepatocarcinogenesis. Mutation Research. 1989;214(1):63-8. DOI: 10.1016/0027-5107(89)90198-x.
21. Kostka G, Urbanek-Olejnik K, Wiadrowska B. Di-butyl phthalate- induced hypomethylation of the c-myc gene in rat liver. Toxicol and Health, 2010;26(7):407-16. DOI: 10.1177/0748233710369124.
22. Babica P, Zurabian R, Kumar ER, Chopra R, Mianecki MJ, Park JS, et al. Methoxychlor and vinclozolin ınduce rapid changes in ıntercellular and ıntracellular signaling in liver progenitor cells. Society of Toxicology. 2016;153(1):174-85. DOI: 10.1093/toxsci/kfw114.
23. Singh S, Li SSL. Epigenetic effects of environmental chemicals bisphenol A and phthalates. International Journal of Molecular Sciences. 2012;13(8):10143-53. DOI: 10.3390/ijms130810143.
24. Suter MA, Aagaard-Tillery KM. Environmental influences on epigenetic profiles. Seminars in Reproductive Medicine. 2009;27(5):380-90. DOI: 10.1055/s-0029-1237426.
25. Palmer JR, Wise LA, Hatch EE, Troisi R, Titus-Ernstoff L, Strohsnitter W, et al. Prenatal diethylstilbestrol exposure and risk of breast cancer. Cancer Epidemiology, Biomarkers and Prevention. 2006;15(8):1509–14. DOI: 10.1158/1055-9965.EPI-06-0109.
26. Anway MD, Cupp AS, Uzumcu M, Skinner MK. Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science. 2005;308(5727):1466–69. DOI: 10.1126/science.1108190.
27. Rey RA, Grinspon RP. Normal male sexual differentiation and aetiology of disorders of sex development. Best Practice and Research. Clinical Endocrinology and Metabolism. 2011;25(2):221–38. DOI: 10.1016/j.beem.2010.08.013.
28. Paustenbach DJ. The US EPA Science Advisory Board evaluation of the EPA dioxin reassessment. Regulatory Toxicology and Pharmacology: RTP. 2002;36(2):211–19. DOI: 10.1006/rtph.2002.1580.
29. Bostrom CE, Gerde P, Hanberg A, Jernstrom B, Johansson C, Kyrklund T, et al. Cancer risk assessment, indicators, and guidelines for polycyclic aromatic hydrocarbons in the ambient air. Environmental Health Perspectives. 2002;110(Suppl. 3):451–88. DOI: 10.1289/ehp.110-1241197.
30. Zhang Y, Dong S, Wang H, Tao S, Kiyama R. Biological impact of environmental polycyclic aromatic hydrocarbons (ePAHs) as endocrine disruptors. Environmental Pollution. 2016;213:809–24. DOI: 10.1016/j. envpol.2016.03.050.
31. Anway MD, Skinner MK. Transgenerational effects of the endocrine disruptor vinclozolin on the prostate transcriptome and adult onset disease. Prostate. 2008;68(5):517–29. DOI: 10.1002/pros.20724.
32. Salnikow K, Zhitkovich A. Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium. Chemical Research in Toxicology. 2008;21(1):28–44. DOI: 10.1021/tx700198a.
33. Vahter ME. Interactions between arsenic-induced toxicity and nutrition in early life. The Journal of Nutrition. 2007;137(12):2798–804. DOI: 10.1093/jn/137.12.2798.
34. https://monographs.iarc.who.int/agents-classified-by-the-iarc/. International Agency for Research on Cancer Classifications. [cited 2024 May 7].
35. Wang T, Lu J, Xu M, Xu Y, Li M, Liu Y, Ning G. Urinary bisphenol a concentration and thyroid function in Chinese adults. Epidemiology.2013;24(2):295-302.
36. Sriphrapradang C, Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. Association between bisphenol A and abnormal free thyroxine level in men. Endocrine.2013; 44:441-447.
37. Stewart PW, Lonky E, Reihman J, Pagano J, Gump BB, Darvill T. The relationship between prenatal PCB exposure and intelligence (IQ) in 9-year-old children. Environmental health perspectives. 2008;116(10):1416-1422.
38. Ramadan M, Cooper B, Posnack NG. Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes. Birth defects research;2020:112(17), 1362-1385.
39. Melzer D, Rice NE, Lewis C, Henley WE, Galloway TS. Association of urinary bisphenol a concentration with heart disease: evidence from NHANES 2003/06. PloS one. 2010;5(1):e8673.
40. LaKind JS, Goodman M, Naiman DQ. Use of NHANES data to link chemical exposures to chronic diseases: a cautionary tale. PloS one. 2012;7(12):e51086.
41. Lind PM, Lind L. Circulating levels of bisphenol A and phthalates are related to carotid atherosclerosis in the elderly. Atherosclerosis. 2011;218(1):207-213.
42. García-Recio E, Costela-Ruiz VJ, Illescas-Montes R, Melguizo- Rodríguez L, García-Martínez O, Ruiz C, De Luna-Bertos E. Modulation of osteogenic gene expression by human osteoblasts cultured in the presence of bisphenols BPF, BPS, or BPAF. International Journal of Molecular Sciences. 2023; 24(5): 4256.
43. Eisa NH, Reddy SV, Elmansi AM, Kondrikova G, Kondrikov D, Shi XM, Hill WD. Kynurenine promotes RANKL-induced osteoclastogenesis in vitro by activating the aryl hydrocarbon receptor pathway. International journal of molecular sciences. 2020;21(21):7931.
44. Tang ZR, Xu XL, Deng SL, Lian ZX, Yu K. Oestrogenic endocrine disruptors in the placenta and the fetus. International journal of molecular sciences. 2020;21(4):1519.
45. Vrachnis N, Loukas N, Vrachnis D, Antonakopoulos N, Zygouris D, Kοlialexi A, Iliodromiti Z. A systematic review of bisphenol A from dietary and non-dietary sources during pregnancy and its possible connection with fetal growth restriction: investigating its potential effects and the window of fetal vulnerability. Nutrients. 2021;13(7):2426.
46. Deji Z, Liu P, Wang X, Zhang X, Luo Y, Huang Z. Association between maternal exposure to perfluoroalkyl and polyfluoroalkyl substances and risks of adverse pregnancy outcomes: A systematic review and meta- analysis. Science of the Total Environment. 2021;783:146984.
47. Grün F, Watanabe H, Zamanian Z, Maeda L, Arima K, Cubacha R, Blumberg B. Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates. Molecular endocrinology. 2006;20(9):2141-2155.
48. Newbold RR, Padilla-Banks E, Snyder RJ, Jefferson WN. Developmental exposure to estrogenic compounds and obesity. Birth Defects Research Part A: Clinical and Molecular Teratology. 2005;73(7):478-480.
49. Hatch EE, Nelson JW, Qureshi MM, Weinberg J, Moore LL, Singer M, Webster TF. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: a cross-sectional study of NHANES data, 1999–2002. Environmental Health. 2008;7:1-15.
50. Ruzzin J, Petersen R, Meugnier E, Madsen L, Lock EJ, Lillefosse H, et al. Persistent organic pollutant exposure leads to insulin resistance syndrome. Environmental health perspectives. 2010;118(4):465-471.
51. Angle BM, Do RP, Ponzi D, Stahlhut RW, Drury BE, Nagel SC, 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. Reproductive toxicology. 2013;42,256-268.
52. Bodin J, Bølling AK, Becher R, Kuper F, Løvik M, Nygaard UC. Transmaternal bisphenol A exposure accelerates diabetes type 1 development in NOD mice. Toxicological Sciences. 2014;137(2): 311- 323.
53. Baker BH, Melough MM, Paquette AG, Barrett ES, Day DB, Kannan K, et al. Ultra-processed and fast food consumption, exposure to phthalates during pregnancy, and socioeconomic disparities in phthalate exposures. Environment international. 2024;183:108427. DOI:10.1016/j.envint.2024.108427.
54. Corbett GA, Lee S, Woodruff TJ, Hanson M, Hod M, Charlesworth AM, et al. International Federation of Gynecology and Obstetrics (FIGO) Committee on Impact of Pregnancy on Long‐term Health and the FIGO Committee on Climate Change and Toxic Environmental Exposures. Nutritional interventions to ameliorate the effect of endocrine disruptors on human reproductive health: A semi‐structured review from FIGO. International Journal of Gynecology & Obstetrics. 2022;157(3),489-501. DOI:10.1002/ijgo.14126.
55. Grun F. Obesogens. Current Opinion in Endocrinology, Diabetes, and Obesity. 2010;17(5): 453–9. DOI: 10.1097/MED.0b013e32833ddea0.
56. Wahlang B, Falkner KC, Gregory B, Ansert D, Young D, Conklin DJ et al. Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice. The Journal of Nutritional Biochemistry. 2013;24(9):1587–95. DOI: 10.1016/j. jnutbio.2013.01.009.
57. Harris DL, Washington MK, Hood DB, Roberts LJ, Ramesh A. Dietary fat-influenced development of colon neoplasia in Apc Min mice exposed to benzo(a)pyrene. Toxicologic Pathology. 2009;37(7):938–46. DOI: 10.1177/0192623309351722.
58. Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. Impaired lipid and glucose homeostasis in hexabromocyclododecane- exposed mice fed a high-fat diet. Environmental Health Perspectives. 2014;122(3):277–83. DOI: 10.1289/ehp.1307421.
59. McGill HC, Jr McMahan CA, Gidding SS. Preventing heart disease in the 21st century: implications of the pathobiological determinants of atherosclerosis in youth (PDAY) study. Circulation. 2008;117(9):1216–27.
60. Perkins JT, Petriello MC, Newsome BJ, Hennig B. Polychlorinated biphenyls and links to cardiovascular disease. Environmental Science and Pollution Research International. 2016;23(3):2160–72. DOI: 10.1007/ s11356-015-4479-6.
61. Petriello MC, Han SG, Newsome BJ, Hennig B. PCB 126 toxicity is modulated by cross-talk between caveolae and Nrf2 signaling. Toxicology and Applied Pharmacology. 2014;277(2):192–9. DOI: 10.1016/j.taap.2014.03.018.
62. Petriello MC, Hoffman JB, Sunkara M, Wahlang B, Perkins JT, Morris AJ, et al. Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro- atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors. The Journal of Nutritional Biochemistry. 2016;33:145–53. DOI: 10.1016/j.jnutbio.2016.03.016.
63. Petriello MC, Newsome B, Hennig B. Influence of nutrition in PCB- induced vascular inflammation. Environmental Science and Pollution Research International. 2014;21(10):6410–8. DOI: 10.1007/s11356-013- 1549-5.
64. D'Angelo S, Scafuro M, Meccariello R. BPA and nutraceuticals, simultaneous effects on endocrine functions. Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets- Immune, Endocrine & Metabolic Disorders). 2019;19(5):594-604. DOI: 10.2174/1871530319666190101120119.
65. Sun TL, Liu Z, Qi ZJ, Huang YP, Gao XQ, Zhang YY. (-)-Epigallocatechin- 3-gallate (EGCG) attenuates arsenic-induced cardiotoxicity in rats. Food and Chemical Toxicology: An International Journal Published for the British Industrial Biological Research Association. 2016;93:102–10. DOI: 10.1016/j.fct.2016.05.004.
66. Newsome BJ, Petriello MC, Han SG, Murphy MO, Eske KE, Sunkara M, et al. Green tea diet decreases PCB 126-induced oxidative stress in mice by up-regulating antioxidant enzymes. The Journal of Nutritional Biochemistry. 2014;25(2):126–35. DOI: 10.1016/j.jnutbio.2013.10.003.
67. Guida N, Laudati G, Anzilotti S, Secondo A, Montuori P, Di Renzo G, et al. Resveratrol via sirtuin-1 downregulates RE1-silencing transcription factor (REST) expression preventing PCB-95-induced neuronal cell death. Toxicology and Applied Pharmacology. 2015;288(3):387–98. DOI: 10.1016/j.taap.2015.08.010.
68. Baker NA, English V, Sunkara M, Morris AJ, Pearson KJ, Cassis LA. Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes. The Journal of Nutritional Biochemistry. 2013;24(12):2168–74. DOI: 10.1016/j. jnutbio.2013.08.009.
69. Yun JM, Jialal I, Devaraj S. Epigenetic regulation of high glucose- induced proinflammatory cytokine production in monocytes by curcumin. The Journal of Nutritional Biochemistry. 2011;22(5):450–8.DOI: 10.1016/j.jnutbio.2010.03.014.
70. Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Advances in Nutrition. 2012;3(1):1–7. DOI: 10.3945/an.111.000893.
71. Sofi F, Cesari F, Abbate R, Gensini GF, Casini A. Adherence to mediterranean diet and health status: meta-analysis. Bmj. 2008;337:a1344. DOI: https://doi.org/10.1136/bmj.a1344.
72. Turunen AW, Jula A, Suominen AL, Mannisto S, Marniemi J, Kiviranta H, et al. Fish consumption, omega-3 fatty acids, and environmental contaminants in relation to low-grade inflammation and early atherosclerosis. Environmental Research. 2013;120:43–54. DOI: 10.1016/j.envres.2012.09.007.
73. Tong H, Rappold AG, Diaz-Sanchez D, Steck SE, Berntsen J, Cascio WE, et al. Omega-3 fatty acid supplementation appears to attenuate particulate air pollution-induced cardiac effects and lipid changes in healthy middle-aged adults. Environmental Health Perspectives. 2012;120(7):952–7. DOI: 10.1289/ehp.1104472.
74. Arguin H, Sanchez M, Bray GA, Lovejoy JC, Peters JC, Jandacek RJ, et al. Impact of adopting a vegan diet or an olestra supplementation on plasma organochlorine concentrations: results from two pilot studies. The British Journal of Nutrition. 2016;103(10):1433–41. DOI: 10.1017/ S000711450999331X.
75. Jandacek RJ, Heubi JE, Buckley DD, Khoury JC, Turner WE, Sjodin A, et al. Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial. The Journal of Nutritional Biochemistry. 2014;25(4):483–8. DOI: 10.1016/j.jnutbio.2014.01.002.
76. Jandacek RJ, Rider T, Keller ER, Tso P. The effect of olestra on the absorption, excretion and storage of 2,2',5,5' tetrachlorobiphenyl; 3,3',4,4' tetrachlorobiphenyl; and perfluorooctanoic acid. Environment International. 2010;36(8):880–3. DOI: 10.1016/j.envint.2009.06.010.
77. Jandacek RJ. Intervention to reduce PCBs: learnings from a controlled study of Anniston residents. Environmental Science and Pollution Research International. 2016;23(3):2022–6. DOI: 10.1007/ s11356-015-4264-6.