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

Autor: Joshua F. Robinson, Aart Verhoef, Jeroen L. A. Pennings, Elisa C.M. Tonk, Aldert H. Piersma, Peter T. Theunissen
Přispěvatelé: Toxicogenomics, Promovendi ODB, RS: GROW - School for Oncology and Reproduction
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Zdroj: Reproductive Toxicology, 41, 57-66. Elsevier Inc.
ISSN: 0890-6238
DOI: 10.1016/j.reprotox.2013.06.069
Popis: 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.
Databáze: OpenAIRE