Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells

Authors

  • B. Lucendo-Villarin Centre for Regenerative Medicine, University of Edinburgh, Edinburgh, UK
  • Patrick Nell IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany
  • Birte Hellwig Department of Statistics, Technical University Dortmund, Dortmund, Germany
  • P. Filis Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
  • David Feuerborn IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany
  • P. J. O'Shaughnessy Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, UK
  • Patricio Godoy IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany
  • Jörg Rahnenführer Department of Statistics, Technical University Dortmund, Dortmund, Germany
  • Jan G. Hengstler IfADo-Leibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund, Dortmund, Germany
  • A. Cherianidou Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Cologne, Germany
  • A. Sachinidis Institute of Neurophysiology and Center for Molecular Medicine Cologne (CMMC), University of Cologne (UKK), Cologne, Germany
  • P. A. Fowler Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
  • David C. Hay Centre for Regenerative Medicine, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, Edinburgh, Scotland, United Kingdom. Telephone +441316519500, Fax +441316519501; E-mail: davehay@talktalk.net

DOI:

https://doi.org/10.17179/excli2020-2934

Keywords:

bisphenol A, bisphenol-F, bisphenol-S, human stem cell, hepatocyte-like cells

Abstract

The debate about possible adverse effects of bisphenol A (BPA) has been ongoing for decades. Bisphenol F (BPF) and S (BPS) have been suggested as “safer” alternatives. In the present study we used hepatocyte-like cells (HLCs) derived from the human embryonic stem cell lines Man12 and H9 to compare the three bisphenol derivatives. Stem cell-derived progenitors were produced using an established system and were exposed to BPA, BPF and BPS for 8 days during their transition to HLCs. Subsequently, we examined cell viability, inhibition of cytochrome P450 (CYP) activity, and genome-wide RNA profiles. Sub-cytotoxic, inhibitory concentrations (IC50) of CYP3A were 20, 9.5 and 25 µM for BPA, BPF and BPS in Man12 derived HLCs, respectively. The corresponding concentrations for H9-derived HLCs were 19, 29 and 31 µM. These IC50 concentrations were used to study global expression changes in this in vitro study and are higher than unconjugated BPA in serum of the general population. A large overlap of up- as well as downregulated genes induced by the three bisphenol derivatives was seen. This is at least 28-fold higher compared to randomly expected gene expression changes. Moreover, highly significant correlations of expression changes induced by the three bisphenol derivatives were obtained in pairwise comparisons. Dysregulated genes were associated with reduced metabolic function, cellular differentiation, embryonic development, cell survival and apoptosis. In conclusion, no major differences in cytochrome inhibitory activities of BPA, BPF and BPS were observed and gene expression changes showed a high degree of similarity.

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Published

2020-11-04

How to Cite

Lucendo-Villarin, B., Nell, P., Hellwig, B., Filis, P., Feuerborn, D., O’Shaughnessy, P. J., … Hay, D. C. (2020). Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells. EXCLI Journal, 19, 1459–1476. https://doi.org/10.17179/excli2020-2934

Issue

Vol. 19 (2020)

Section

Original articles

License

Copyright (c) 2020 B. Lucendo-Villarin, Patrick Nell, Birte Hellwig, P. Filis, David Feuerborn, P. J. O'Shaughnessy, Patricio Godoy, Jörg Rahnenführer, Jan G. Hengstler, A. Cherianidou, A. Sachinidis, P. A. Fowler, David C. Hay

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