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Title: Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation

Abstract

The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomicsmore » was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.« less

Authors:
 [1];  [2];  [3];  [1];  [2];  [4];  [1];  [1];  [3]
  1. Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands)
  2. (Netherlands)
  3. (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht (Netherlands)
  4. Centre for Environmental Quality, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven (Netherlands)
Publication Date:
OSTI Identifier:
22285406
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 272; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BIOLOGICAL MARKERS; CAFFEINE; CONCENTRATION RATIO; EMBRYOS; GENES; RETINOIC ACID; SACCHARIN; SENSITIVITY; TOXICITY

Citation Formats

Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl, Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Institute for Risk Assessment Sciences, Pronk, Tessa E., Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Brandhof, Evert-Jan van den, Ven, Leo T.M. van der, Piersma, Aldert H., and Institute for Risk Assessment Sciences. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation. United States: N. p., 2013. Web. doi:10.1016/J.TAAP.2013.05.037.
Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl, Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Institute for Risk Assessment Sciences, Pronk, Tessa E., Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Brandhof, Evert-Jan van den, Ven, Leo T.M. van der, Piersma, Aldert H., & Institute for Risk Assessment Sciences. Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation. United States. doi:10.1016/J.TAAP.2013.05.037.
Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl, Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Institute for Risk Assessment Sciences, Pronk, Tessa E., Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, Brandhof, Evert-Jan van den, Ven, Leo T.M. van der, Piersma, Aldert H., and Institute for Risk Assessment Sciences. Tue . "Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation". United States. doi:10.1016/J.TAAP.2013.05.037.
@article{osti_22285406,
title = {Transcriptomic analysis in the developing zebrafish embryo after compound exposure: Individual gene expression and pathway regulation},
author = {Hermsen, Sanne A.B., E-mail: Sanne.Hermsen@rivm.nl and Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht and Institute for Risk Assessment Sciences and Pronk, Tessa E. and Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht and Brandhof, Evert-Jan van den and Ven, Leo T.M. van der and Piersma, Aldert H. and Institute for Risk Assessment Sciences},
abstractNote = {The zebrafish embryotoxicity test is a promising alternative assay for developmental toxicity. Classically, morphological assessment of the embryos is applied to evaluate the effects of compound exposure. However, by applying differential gene expression analysis the sensitivity and predictability of the test may be increased. For defining gene expression signatures of developmental toxicity, we explored the possibility of using gene expression signatures of compound exposures based on commonly expressed individual genes as well as based on regulated gene pathways. Four developmental toxic compounds were tested in concentration-response design, caffeine, carbamazepine, retinoic acid and valproic acid, and two non-embryotoxic compounds, D-mannitol and saccharin, were included. With transcriptomic analyses we were able to identify commonly expressed genes, which were mostly development related, after exposure to the embryotoxicants. We also identified gene pathways regulated by the embryotoxicants, suggestive of their modes of action. Furthermore, whereas pathways may be regulated by all compounds, individual gene expression within these pathways can differ for each compound. Overall, the present study suggests that the use of individual gene expression signatures as well as pathway regulation may be useful starting points for defining gene biomarkers for predicting embryotoxicity. - Highlights: • The zebrafish embryotoxicity test in combination with transcriptomics was used. • We explored two approaches of defining gene biomarkers for developmental toxicity. • Four compounds in concentration-response design were tested. • We identified commonly expressed individual genes as well as regulated gene pathways. • Both approaches seem suitable starting points for defining gene biomarkers.},
doi = {10.1016/J.TAAP.2013.05.037},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 272,
place = {United States},
year = {2013},
month = {10}
}