Metabolomics

, 14:45 | Cite as

A systematic review of metabolomics biomarkers for Bisphenol A exposure

Review Article
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Accepted:

Abstract

Introduction

Bisphenol A (BPA), 2,2-bis(4-hydroxyphenyl) propane, a common industrial chemical which has extremely huge production worldwide, is ubiquitous in the environment. Human have high risk of exposing to BPA and the health problems caused by BPA exposure have aroused public concern. However, the biomarkers for BPA exposure are lacking. As a rapidly developing subject, metabolomics has accumulated a large amount of valuable data in various fields. The secondary application of published metabolomics data could be a very promising field for generating novel biomarkers whilst further understanding of toxicity mechanisms.

Objectives

To summarize the published literature on the use of metabolomics as a tool to study BPA exposure and provide a systematic perspectives of current research on biomarkers screening of BPA exposure.

Methods

We conducted a systematic search of MEDLINE (PubMed) up to the end of June 25, 2017 with the key term combinations of ‘metabolomics’, ‘metabonomics’, ‘mass spectrometry’, ‘nuclear magnetic spectroscopy’, ‘metabolic profiling’ and ‘amino acid profile’ combined with ‘BPA exposure’. Additional articles were identified through searching the reference lists from included studies.

Results

This systematic review included 15 articles. Intermediates of glycolysis, Krebs cycle, β oxidation of long chain fatty acids, pentose phosphate pathway, nucleoside metabolism, branched chain amino acid metabolism, aromatic amino acids metabolism, sulfur-containing amino acids metabolism were significantly changed after BPA exposure, suggesting BPA had a highly complex toxic effects on organism which was consistent with existing studies. The biomarkers most consistently associated with BPA exposure were lactate and choline.

Conclusion

Existing metabolomics studies of BPA exposure present heterogeneous findings regarding metabolite profile characteristics. We need more evidence from target metabolomics and epidemiological studies to further examine the reliability of these biomarkers which link to low, environmentally relevant, exposure of BPA in human body.

Keywords

BPA Metabolomics Biomarkers Environmental exposure Review 
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Notes

Compliance with ethical standards

Conflict of interest

All the authors declare no conflict of interest.

Ethical approval

This review was conducted in accordance with ethical standards.

Supplementary material

11306_2018_1342_MOESM1_ESM.docx (15 kb)
Supplementary material 1 (DOCX 15 KB)

References

  1. Acevedo, N., Davis, B., Schaeberle, C. M., Sonnenschein, C., & Soto, A. M. (2013). Perinatally administered bisphenol a as a potential mammary gland carcinogen in rats. Environmental Health Perspectives, 121(9), 1040–1046.PubMedPubMedCentralGoogle Scholar
  2. Alonso-Magdalena, P., Quesada, I., & Nadal, Á (2015). Prenatal exposure to BPA and offspring outcomes: The diabesogenic behavior of BPA. Dose Response, 13(2), 1559325815590395.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Ankley, G. T., & Villeneuve, D. L. (2006). The fathead minnow in aquatic toxicology: Past, present and future. Aquatic Toxicology, 78(1), 91–102.CrossRefPubMedGoogle Scholar
  4. Bauer, S. M., Roy, A., Emo, J., Chapman, T. J., Georas, S. N., & Lawrence, B. P. (2012). The effects of maternal exposure to bisphenol A on allergic lung inflammation into adulthood. Toxicological Sciences, 130(1), 82–93.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Braun, J. M., Muckle, G., Arbuckle, T., Bouchard, M. F., Fraser, W. D., Ouellet, E., et al. (2017). Associations of prenatal urinary bisphenol A concentrations with child behaviors and cognitive abilities. Environmental Health Perspectives, 125(6), 067008.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Breen, A. P., & Murphy, J. A. (1995). Reactions of oxyl radicals with DNA. Free Radical Biology and Medicine, 18(6), 1033–1077.CrossRefPubMedGoogle Scholar
  7. Cabaton, N. J., Canlet, C., Wadia, P. R., Tremblay-Franco, M., Gautier, R., Molina, J., et al. (2013). Effects of low doses of bisphenol A on the metabolome of perinatally exposed CD-1 mice. Environmental Health Perspectives, 121(5), 586–593.PubMedPubMedCentralGoogle Scholar
  8. Calafat, A. M., Ye, X., Wong, L. Y., Reidy, J. A., & Needham, L. L. (2008). Exposure of the U.S. population to bisphenol A and 4-tertiary-octylphenol: 2003–2004. Environmental Health Perspectives, 116(1), 39–44.CrossRefPubMedGoogle Scholar
  9. Chen, M., Xu, B., Ji, W., Qiao, S., Hu, N., Hu, Y., et al. (2012). Bisphenol A alters n-6 fatty acid composition and decreases antioxidant enzyme levels in rat testes: A LC-QTOF-based metabolomics study. PLoS ONE, 7(9), e44754.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Chen, M., Zhou, K., Chen, X., Qiao, S., Hu, Y., Xu, B., et al. (2014). Metabolomic analysis reveals metabolic changes caused by bisphenol A in rats. Toxicological Sciences, 138(2), 256–267.CrossRefPubMedGoogle Scholar
  11. Cheng, S., Rhee, E. P., Larson, M. G., Lewis, G. D., McCabe, E. L., Shen, D., et al. (2012). Metabolite profiling identifies pathways associated with metabolic risk in humans. Circulation, 125(18), 2222–2231.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Cho, S. H., Choi, M. H., Kwon, O. S., Lee, W. Y., & Chung, B. C. (2009). Metabolic significance of bisphenol A-induced oxidative stress in rat urine measured by liquid chromatography-mass spectrometry. Journal of Applied Toxicology, 29(2), 110–117.CrossRefPubMedGoogle Scholar
  13. Collette, T. W., Skelton, D. M., Davis, J. M., Cavallin, J. E., Jensen, K. M., Kahl, M. D., et al. (2016). Metabolite profiles of repeatedly sampled urine from male fathead minnows (Pimephales promelas) contain unique lipid signatures following exposure to anti-androgens. Comparative Biochemistry and Physiology Part D: Genomics and Proteomics, 19, 190–198.Google Scholar
  14. Corrales, J., Kristofco, L. A., Steele, W. B., Yates, B. S., Breed, C. S., Williams, E. S., & Brooks, B. W. (2015). Global assessment of bisphenol A in the environment: Review and analysis of its occurrence and bioaccumulation. Dose Response, 13(3), 1559325815598308.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Dizdaroglu, M. (1992). Oxidative damage to DNA in mammalian chromatin. Mutation Research, 275(3–6), 331–342.CrossRefPubMedGoogle Scholar
  16. Ekman, D. R., Hartig, P. C., Cardon, M., Skelton, D. M., Teng, Q., Durhan, E. J., et al. (2012). Metabolite profiling and a transcriptional activation assay provide direct evidence of androgen receptor antagonism by bisphenol A in fish. Environmental Science & Technology, 46(17), 9673–9680.CrossRefGoogle Scholar
  17. Ekman, D. R., Skelton, D. M., Davis, J. M., Villeneuve, D. L., Cavallin, J. E., Schroeder, A., et al. (2015). Metabolite profiling of fish skin mucus: A novel approach for minimally-invasive environmental exposure monitoring and surveillance. Environmental Science & Technology, 49(5), 3091–3100.CrossRefGoogle Scholar
  18. Fic, A., Žegura, B., Dolenc, M. S., Filipič, M., & Peterlin, M. L. (2013). Mutagenicity and DNA damage of bisphenol A and its structural analogues in HepG2 cells. Archives of Industrial Hygiene and Toxicology, 64(2), 189–200.CrossRefPubMedGoogle Scholar
  19. Friedrich, N. (2012). Metabolomics in diabetes research. Journal of Endocrinology, 215(1), 29–42.CrossRefPubMedGoogle Scholar
  20. Hoepner, L. A., Whyatt, R. M., Widen, E. M., Hassoun, A., Oberfield, S. E., Mueller, N. T., et al. (2016). Bisphenol A and adiposity in an inner-city birth cohort. Environmental Health Perspectives, 124(10), 1644–1650.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Hu, W., Dong, T., Wang, L., Guan, Q., Song, L., Chen, D., et al. (2017). Obesity aggravates toxic effect of BPA on spermatogenesis. Environment International, 105, 56–65.CrossRefPubMedGoogle Scholar
  22. Huang, B., Jiang, C., Luo, J., Cui, Y., Qin, L., & Liu, J. (2014). Maternal exposure to bisphenol A may increase the risks of Parkinson’s disease through down-regulation of fetal IGF-1 expression. Medical Hypotheses, 82(3), 245–249.CrossRefPubMedGoogle Scholar
  23. Huynh, J., Xiong, G., & Bentleylewis, R. (2014). A systematic review of metabolite profiling in gestational diabetes mellitus. Diabetologia, 57(12), 2453–2464.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Ji, C., Wei, L., Zhao, J., & Wu, H. (2014). Metabolomic analysis revealed that female mussel Mytilus galloprovincialis was sensitive to bisphenol A exposures. Environmental Toxicology and Pharmacology, 37(2), 844–849.CrossRefPubMedGoogle Scholar
  25. Jordan, J., Zare, A., Jackson, L. J., Habibi, H. R., & Weljie, A. M. (2012). Environmental contaminant mixtures at ambient concentrations invoke a metabolic stress response in goldfish not predicted from exposure to individual compounds alone. Journal of Proteome Research, 11(2), 1133–1143.CrossRefPubMedGoogle Scholar
  26. Lassen, T. H., Frederiksen, H., Jensen, T. K., Petersen, J. H., Joensen, U. N., Main, K. M., et al. (2014). Urinary bisphenol A levels in young men: Association with reproductive hormones and semen quality. Environmental Health Perspectives, 122(5), 478–484.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Li, D. K., Zhou, Z., Miao, M., He, Y., Wang, J., Ferber, J., et al. (2011). Urine bisphenol-A (BPA) level in relation to semen quality. Fertility and Sterility, 95(2):625–630.CrossRefPubMedGoogle Scholar
  28. Li, S., Jin, Y., Wang, J., Tang, Z., Xu, S., Wang, T., & Cai, Z. (2016). Urinary profiling of cis-diol-containing metabolites in rats with bisphenol A exposure by liquid chromatography-mass spectrometry and isotope labeling. Analyst, 141(3), 1144–1153.CrossRefPubMedGoogle Scholar
  29. Lotta, L. A., Scott, R. A., Sharp, S. J., Burgess, S., Luan, J., Tillin, T., et al. (2016). Genetic predisposition to an impaired metabolism of the branched-chain amino acids and risk of type 2 diabetes: A mendelian randomisation analysis. PLoS Medicine, 13(11), e1002179.CrossRefPubMedPubMedCentralGoogle Scholar
  30. McCormack, S. E., Shaham, O., McCarthy, M. A., Deik, A. A., Wang, T. J., Gerszten, R. E., et al. (2013). Circulating branched-chain amino acid concentrations are associated with obesity and future insulin resistance in children and adolescents. Pediatric Obesity, 8(1), 52–61.CrossRefPubMedGoogle Scholar
  31. Mokra, K., Kuźmińska-Surowaniec, A., Woźniak, K., & Michałowicz, J. (2017). Evaluation of DNA-damaging potential of bisphenol A and its selected analogs in human peripheral blood mononuclear cells (in vitro study). Food and Chemical Toxicology, 100, 62–69.CrossRefPubMedGoogle Scholar
  32. Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., et al. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metabolism, 9(4), 311–326.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Ortmayr, K., Schwaiger, M., Hann, S., & Koellensperger, G. (2015). An integrated metabolomics workflow for the quantification of sulfur pathway intermediates employing thiol protection with N-ethyl maleimide and hydrophilic interaction liquid chromatography tandem mass spectrometry. Analyst, 140(22), 7687–7695.CrossRefPubMedGoogle Scholar
  34. Pfeifer, D., Chung, Y. M., & Hu, M. C. (2015). Effects of low-dose bisphenol A on DNA damage and proliferation of breast cells: The role of c-Myc. Environmental Health Perspectives, 123(12), 1271–1279.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Potratz, S., Tarnow, P., Jungnickel, H., Baumann, S., von Bergen, M., Tralau, T., & Luch, A. (2017). Combination of metabolomics with cellular assays reveals new biomarkers and mechanistic insights on xenoestrogenic exposures in MCF-7 cells. Chemical Research in Toxicology, 30(4), 883–892.CrossRefPubMedGoogle Scholar
  36. Poulsen, H. E., Prieme, H., & Loft, S. (1998). Role of oxidative DNA damage in cancer initiation and promotion. European Journal of Cancer Prevention, 7(1), 9–16.PubMedGoogle Scholar
  37. Prins, G. S., Ye, S. H., Birch, L., Zhang, X., Cheong, A., Lin, H., et al. (2017). Prostate cancer risk and DNA methylation signatures in aging rats following developmental BPA exposure: A dose-response analysis. Environmental Health Perspectives, 125(7), 077007.CrossRefPubMedPubMedCentralGoogle Scholar
  38. Rahman, M. S., Kwon, W. S., Karmakar, P. C., Yoon, S. J., Ryu, B. Y., & Pang, M. G. (2017). Gestational exposure to bisphenol A affects the function and proteome profile of F1 spermatozoa in adult mice. Environmental Health Perspectives, 125(2), 238–245.PubMedGoogle Scholar
  39. Roberts, L. D., Koulman, A., & Griffin, J. L. (2014). Towards metabolic biomarkers of insulin resistance and type 2 diabetes: Progress from the metabolome. The Lancet Diabetes & Endocrinology, 2(1), 65–75.CrossRefGoogle Scholar
  40. Rochester, J. R. (2013). Bisphenol A and human health: A review of the literature. Reproductive Toxicology, 42, 132–155.CrossRefPubMedGoogle Scholar
  41. Rosenfeld, C. S., Sieli, P. T., Warzak, D. A., Ellersieck, M. R., Pennington, K. A., & Roberts, R. M. (2013). Maternal exposure to bisphenol A and genistein has minimal effect on A(vy)/a offspring coat color but favors birth of agouti over nonagouti mice. Proceedings of the National Academy of Sciences, 110(2), 537–542.CrossRefGoogle Scholar
  42. Snijder, C. A., Heederik, D., Pierik, F. H., Hofman, A., Jaddoe, V. W., Koch, H. M., et al. (2013). Fetal growth and prenatal exposure to bisphenol A: The generation R study. Environmental Health Perspectives, 121(3), 393–398.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Soto, A. M., Brisken, C., Schaeberle, C., & Sonnenschein, C. (2013). Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. Journal of Mammary Gland Biology and Neoplasia, 18(2), 199–208.CrossRefPubMedPubMedCentralGoogle Scholar
  44. Sun, H., & Wang, Y. (2016). Branched chain amino acid metabolic reprogramming in heart failure. Biochimica et Biophysica Acta, 1862(12), 2270–2275.CrossRefPubMedGoogle Scholar
  45. Susiarjo, M., Xin, F., Stefaniak, M., Mesaros, C., Simmons, R. A., & Bartolomei, M. S. (2017). Bile acids and tryptophan metabolism are novel pathways involved in metabolic abnormalities in BPA-exposed pregnant mice and male offspring. Endocrinology, 158(8), 2533–2542.CrossRefPubMedGoogle Scholar
  46. Van Winkle, L. S., Murphy, S. R., Boetticher, M. V., & VandeVoort, C. A. (2013). Fetal exposure of rhesus macaques to bisphenol a alters cellular development of the conducting airway by changing epithelial secretory product expression. Environmental Health Perspectives, 121(8), 912–918.CrossRefPubMedPubMedCentralGoogle Scholar
  47. Wang, T. J., Larson, M. G., Vasan, R. S., Cheng, S., Rhee, E. P., McCabe, E., et al. (2011). Metabolite profiles and the risk of developing diabetes. Nature Medicine, 17(4), 448–453.CrossRefPubMedPubMedCentralGoogle Scholar
  48. Weinhouse, C., Anderson, O. S., Bergin, I. L., Vandenbergh, D. J., Gyekis, J. P., Dingman, M. A., et al. (2014). Dose-dependent incidence of hepatic tumors in adult mice following perinatal exposure to bisphenol A. Environmental Health Perspectives, 122(5), 485–491.PubMedPubMedCentralGoogle Scholar
  49. Yoon, C., Yoon, D., Cho, J., Kim, S., Lee, H., Choi, H., & Kim, S. (2017). 1H-NMR-based metabolomic studies of bisphenol A in zebrafish (Danio rerio). Journal of Environmental Science and Health, Part B, 52(4), 282–289.CrossRefGoogle Scholar
  50. Zeng, J., Kuang, H., Hu, C., Shi, X., Yan, M., Xu, L., et al. (2013). Effect of bisphenol A on rat metabolic profiling studied by using capillary electrophoresis time-of-flight mass spectrometry. Environmental Science & Technology, 47(13), 7457–7465.CrossRefGoogle Scholar
  51. Zhang, T., Sun, H., & Kannan, K. (2013). Blood and urinary bisphenol A concentrations in children, adults, and pregnant women from china: Partitioning between blood and urine and maternal and fetal cord blood. Environmental Science & Technology, 47(9), 4686–4694.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Computer Science and TechnologyHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  2. 2.Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  3. 3.School of Public HealthUniversity of South ChinaHengyangPeople’s Republic of China
  4. 4.School of Computer and Information TechnologyXinyang Normal UniversityXinyangPeople’s Republic of China

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