Cargando…
Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells
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 t...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Leibniz Research Centre for Working Environment and Human Factors
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726493/ https://www.ncbi.nlm.nih.gov/pubmed/33312107 http://dx.doi.org/10.17179/excli2020-2934 |
_version_ | 1783620900945395712 |
---|---|
author | Lucendo-Villarin, B. Nell, P. Hellwig, B. Filis, P. Feuerborn, D. O'Shaughnessy, P.J. Godoy, P. Rahnenführer, J. Hengstler, J.G. Cherianidou, A. Sachinidis, A. Fowler, P.A. Hay, D.C. |
author_facet | Lucendo-Villarin, B. Nell, P. Hellwig, B. Filis, P. Feuerborn, D. O'Shaughnessy, P.J. Godoy, P. Rahnenführer, J. Hengstler, J.G. Cherianidou, A. Sachinidis, A. Fowler, P.A. Hay, D.C. |
author_sort | Lucendo-Villarin, B. |
collection | PubMed |
description | 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 (IC(50)) 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 IC(50) 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. |
format | Online Article Text |
id | pubmed-7726493 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Leibniz Research Centre for Working Environment and Human Factors |
record_format | MEDLINE/PubMed |
spelling | pubmed-77264932020-12-10 Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells Lucendo-Villarin, B. Nell, P. Hellwig, B. Filis, P. Feuerborn, D. O'Shaughnessy, P.J. Godoy, P. Rahnenführer, J. Hengstler, J.G. Cherianidou, A. Sachinidis, A. Fowler, P.A. Hay, D.C. EXCLI J Original Article 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 (IC(50)) 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 IC(50) 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. Leibniz Research Centre for Working Environment and Human Factors 2020-11-04 /pmc/articles/PMC7726493/ /pubmed/33312107 http://dx.doi.org/10.17179/excli2020-2934 Text en Copyright © 2020 Lucendo-Villarin et al. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/4.0/) You are free to copy, distribute and transmit the work, provided the original author and source are credited. |
spellingShingle | Original Article Lucendo-Villarin, B. Nell, P. Hellwig, B. Filis, P. Feuerborn, D. O'Shaughnessy, P.J. Godoy, P. Rahnenführer, J. Hengstler, J.G. Cherianidou, A. Sachinidis, A. Fowler, P.A. Hay, D.C. Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells |
title | Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells |
title_full | Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells |
title_fullStr | Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells |
title_full_unstemmed | Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells |
title_short | Genome-wide expression changes induced by bisphenol A, F and S in human stem cell derived hepatocyte-like cells |
title_sort | genome-wide expression changes induced by bisphenol a, f and s in human stem cell derived hepatocyte-like cells |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726493/ https://www.ncbi.nlm.nih.gov/pubmed/33312107 http://dx.doi.org/10.17179/excli2020-2934 |
work_keys_str_mv | AT lucendovillarinb genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT nellp genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT hellwigb genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT filisp genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT feuerbornd genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT oshaughnessypj genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT godoyp genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT rahnenfuhrerj genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT hengstlerjg genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT cherianidoua genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT sachinidisa genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT fowlerpa genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells AT haydc genomewideexpressionchangesinducedbybisphenolafandsinhumanstemcellderivedhepatocytelikecells |