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.
authors.affiliation: Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), P.O. Box 1, 3720 BA Bilthoven, The Netherlands; Department of Toxicogenomics, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands; Institute for Risk Assessment Sciences (IRAS), Utrecht University, P.O. Box 80.178, 3508 TD, Utrecht, The Netherlands. Electronic address: Sanne.Hermsen@rivm.nl.
authors.forename: Sanne A B
authors.initials: SA
authors.lastname: Hermsen
authors.forename: Tessa E
authors.initials: TE
authors.lastname: Pronk
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: van den Brandhof
authors.forename: Leo T M
authors.initials: LT
authors.lastname: van der Ven
authors.forename: Aldert H
authors.initials: AH
authors.lastname: Piersma
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers; D002110:Caffeine / Q000378:metabolism / Q000633:toxicity; D002220:Carbamazepine / Q000378:metabolism / Q000633:toxicity; D000697:Central Nervous System Stimulants / Q000378:metabolism / Q000633:toxicity; D004625:Embryo, Nonmammalian / Q000033:anatomy & histology / Q000502:physiology*; D047108:Embryonic Development / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D046228:Microarray Analysis; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D015398:Signal Transduction / Q000187:drug effects; D013723:Teratogens / Q000633:toxicity*; D059467:Transcriptome / Q000235:genetics*
chemical_list: D015415:Biomarkers; D000697:Central Nervous System Stimulants; D013723:Teratogens; D002220:Carbamazepine; D002110:Caffeine; D012313:RNA
keywords: Alternative; Developmental toxicity; Gene expression; Pathway analysis; Transcriptomics; Zebrafish embryo