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

Sanne A. B. Hermsen*, Tessa E. Pronk, Evert-Jan van den Brandhof, Leo T. M. van der Ven, Aldert H. Piersma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

30 Citations (Web of Science)

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, p-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.
Original languageEnglish
Pages (from-to)161-171
JournalToxicology and Applied Pharmacology
Volume272
Issue number1
DOIs
Publication statusPublished - 1 Oct 2013

Keywords

  • Zebrafish embryo
  • Developmental toxicity
  • Alternative
  • Transcriptomics
  • Gene expression
  • Pathway analysis

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