Valproic acid-induced gene expression responses in rat whole embryo culture and comparison across in vitro developmental and non-developmental models

Ilse Tonk*, Joshua F. Robinson, Aart Verhoef, Peter T. Theunissen, Jeroen L. A. Pennings, Aldert H. Piersma

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Transcriptomic evaluations may improve toxicity prediction of in vitro-based developmental models. In this study, transcriptomics was used to identify VPA-induced gene expression changes in rat whole embryo culture (WEC). Furthermore, VPA-induced responses were compared across in vitro-based developmental models, such as the cardiac and neural embryonic stem cells (ESTc and ESTn, respectively) and the zebrafish embryotoxicity model. VPA-induced gene regulation in WEC corresponded with observed morphological effects and previously suggested mechanisms of toxicity. Gene Ontology term-directed analysis showed conservation of VPA-induced gene expression changes across in vitro-based developmental models, with ESTc and ESTn exhibiting complementary responses. Furthermore, comparison of in vitro-based developmental and non-developmental models revealed that more generalized VPA-induced effects can be detected using non-developmental models whereas developmental models provide added value when assessing developmental-specific effects. These analyses can be used to optimize test batteries for the detection of developmental toxicants in vitro.
Original languageEnglish
Pages (from-to)57-66
JournalReproductive Toxicology
Publication statusPublished - Nov 2013


  • Embryo
  • Transcriptomics
  • Gene expression
  • Valproic acid
  • Whole embryo culture
  • In vitro

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