A systematic review of metabolomics biomarkers for Bisphenol A exposure
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.
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.
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.
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.
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.
KeywordsBPA Metabolomics Biomarkers Environmental exposure Review
Compliance with ethical standards
Conflict of interest
All the authors declare no conflict of interest.
This review was conducted in accordance with ethical standards.
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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