Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A
Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L−1, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at the exposed animals, well below the macroscopic LOEC, but related to at least some of the observed morphological alterations, particularly in eye size and yolk sac resorption. Our data supports the idea that the physiological effects of BPA cannot be only explained by its rather weak interaction with the estrogen receptor, and that multivariate analyses are required to analyze the effects of toxicants like BPA, which interact with different cellular targets producing complex phenotypes. Estrogenic- and retinoid-like transcriptomic effects of bisphenol A in zebrafish eleutheroembryos and their relationship with morphological alterations. © 2018 Elsevier Ltd
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Format: | artículo biblioteca |
Language: | English |
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Elsevier
2018-12
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Subjects: | ANOVA-PLS, BPA, Differentially expressed genes (DEGs), Hormone-response, Obesogens, RNA-Seq, |
Online Access: | http://hdl.handle.net/10261/177128 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100000781 |
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dig-idaea-es-10261-1771282021-11-10T10:18:03Z Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A Martínez, Rubén Esteve-Codina, Anna Herrero-Nogareda, Laia Ortiz-Villanueva, Elena Barata Martí, Carlos Tauler, Romà Raldúa, Demetrio Piña, Benjamín Navarro-Martín, Laia European Research Council Ministerio de Economía y Competitividad (España) Ortiz-Villanueva, Elena [0000-0001-5358-8934] Barata, Carlos [0000-0002-3360-0729] Tauler, Romà [0000-0001-8559-9670] Raldúa, Demetrio [0000-0001-5256-1641] Piña, Benjamin [0000-0001-9216-2768] Navarro-Martín, Laia [0000-0001-6554-8833] ANOVA-PLS BPA Differentially expressed genes (DEGs) Hormone-response Obesogens RNA-Seq Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L−1, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at the exposed animals, well below the macroscopic LOEC, but related to at least some of the observed morphological alterations, particularly in eye size and yolk sac resorption. Our data supports the idea that the physiological effects of BPA cannot be only explained by its rather weak interaction with the estrogen receptor, and that multivariate analyses are required to analyze the effects of toxicants like BPA, which interact with different cellular targets producing complex phenotypes. Estrogenic- and retinoid-like transcriptomic effects of bisphenol A in zebrafish eleutheroembryos and their relationship with morphological alterations. © 2018 Elsevier Ltd This work was supported by the European Research Council under the European Union's Seventh Framework Programme ( FP/2007–2013 )/ERC Grant Agreement n. 320737 . Some part of this study was also supported by a grant from the Spanish Ministry of Economy and Competitiveness ( CTQ2014-56777-R ) and by a grant ( PT17/0009/0019 ) from ISCIII (Carlos III Health Institute), part of the Spanish Ministry of Economy and Competitiveness, and cofinanced by the European Regional Development Fund (ERDF). LNM was supported by a Beatriu de Pinos Postdoctoral Fellow ( 2013BP-B-00088 ) awarded by the Secretary for Universities and Research of the Ministry of Economy and Knowledge of the Government of Catalonia and the Cofund programme of the Marie Curie Actions of the 7th R&D Framework Programme of the European Union. RM was supported by a FPU predoctoral fellow from the Spanish Ministry of Education, Culture and Sport (ref. FPU15/03332 ). We would like to thank Ms. Elia Martinez-Prats and David Angelats for helping with the real time qRT-PCRs measurements. Appendix A Peer reviewed 2019-03-04T08:07:58Z 2019-03-04T08:07:58Z 2018-12 artículo http://purl.org/coar/resource_type/c_6501 Environmental Pollution 243: 988-997 (2018) http://hdl.handle.net/10261/177128 10.1016/j.envpol.2018.09.043 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100000781 en #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/EC/FP7/320737 info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/CTQ2014-56777-R Postprint https://doi.org/10.1016/j.envpol.2018.09.043 Sí open Elsevier |
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ANOVA-PLS BPA Differentially expressed genes (DEGs) Hormone-response Obesogens RNA-Seq ANOVA-PLS BPA Differentially expressed genes (DEGs) Hormone-response Obesogens RNA-Seq |
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ANOVA-PLS BPA Differentially expressed genes (DEGs) Hormone-response Obesogens RNA-Seq ANOVA-PLS BPA Differentially expressed genes (DEGs) Hormone-response Obesogens RNA-Seq Martínez, Rubén Esteve-Codina, Anna Herrero-Nogareda, Laia Ortiz-Villanueva, Elena Barata Martí, Carlos Tauler, Romà Raldúa, Demetrio Piña, Benjamín Navarro-Martín, Laia Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A |
description |
Despite the abundant literature on the adverse effects of Bisphenol A (BPA) as endocrine disruptor, its toxicity mechanisms are still poorly understood. We present here a study of its effects on the zebrafish eleutheroembryo transcriptome at concentrations ranging from 0.1 to 4 mg L−1, this latter representing the lowest observed effect concentration (LOEC) found in our study at three different macroscopical endpoints (survival, hatching and swim bladder inflation). Multivariate data analysis methods identified both monotonic and bi-phasic patterns of dose-dependent responses. Functional analyses of genes affected by BPA exposure suggest an interaction of BPA with different signaling pathways, being the estrogenic and retinoid receptors two likely targets. In addition, we identified an apparently unrelated inhibitory effect on, among others, visual function genes. We interpret our data as the result of a sum of underlying, independent molecular mechanisms occurring simultaneously at the exposed animals, well below the macroscopic LOEC, but related to at least some of the observed morphological alterations, particularly in eye size and yolk sac resorption. Our data supports the idea that the physiological effects of BPA cannot be only explained by its rather weak interaction with the estrogen receptor, and that multivariate analyses are required to analyze the effects of toxicants like BPA, which interact with different cellular targets producing complex phenotypes. Estrogenic- and retinoid-like transcriptomic effects of bisphenol A in zebrafish eleutheroembryos and their relationship with morphological alterations. © 2018 Elsevier Ltd |
author2 |
European Research Council |
author_facet |
European Research Council Martínez, Rubén Esteve-Codina, Anna Herrero-Nogareda, Laia Ortiz-Villanueva, Elena Barata Martí, Carlos Tauler, Romà Raldúa, Demetrio Piña, Benjamín Navarro-Martín, Laia |
format |
artículo |
topic_facet |
ANOVA-PLS BPA Differentially expressed genes (DEGs) Hormone-response Obesogens RNA-Seq |
author |
Martínez, Rubén Esteve-Codina, Anna Herrero-Nogareda, Laia Ortiz-Villanueva, Elena Barata Martí, Carlos Tauler, Romà Raldúa, Demetrio Piña, Benjamín Navarro-Martín, Laia |
author_sort |
Martínez, Rubén |
title |
Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A |
title_short |
Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A |
title_full |
Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A |
title_fullStr |
Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A |
title_full_unstemmed |
Dose-dependent transcriptomic responses of zebrafish eleutheroembryos to Bisphenol A |
title_sort |
dose-dependent transcriptomic responses of zebrafish eleutheroembryos to bisphenol a |
publisher |
Elsevier |
publishDate |
2018-12 |
url |
http://hdl.handle.net/10261/177128 http://dx.doi.org/10.13039/501100003329 http://dx.doi.org/10.13039/501100000781 |
work_keys_str_mv |
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