The Transcriptome of the Zebrafish Embryo After Chemical Exposure: A Meta-Analysis

Abstract

Numerous studies have been published in the past years investigating the transcriptome of the zebrafish embryo (ZFE) upon being subjected to chemical stress. Aiming at a more mechanistic understanding of the results of such studies, knowledge about commonalities of transcript regulation in response to chemical stress is needed. Thus, our goal in this study was to identify and interpret genes and gene sets constituting a general response to chemical exposure. Therefore, we aggregated and reanalyzed published toxicogenomics data obtained with the ZFE. We found that overlap of differentially transcribed genes in response to chemical stress across independent studies is generally low and the most commonly differentially transcribed genes appear in less than 50% of all treatments across studies. However, effect size analysis revealed several genes showing a common trend of differential expression, among which genes related to calcium homeostasis emerged as key, especially in exposure settings up to 24 h post-fertilization. Additionally, we found that these and other downregulated genes are often linked to anatomical regions developing during the respective exposure period. Genes showing a trend of increased expression were, among others, linked to signaling pathways (e.g., Wnt, Fgf) as well as lysosomal structures and apoptosis. The findings of this study help to increase the understanding of chemical stress responses in the developing zebrafish embryo and provide a starting point to improve experimental designs for this model system. In future, improved time- and concentration-resolved experiments should offer better understanding of stress response patterns and access to mechanistic information.

Map and model—moving from observation to prediction in toxicogenomics

“…Fig. S8) one should be aware of the limitations of such comparisons due to differences in experimental factors as discussed by Schüttler et al [18]. Here, we show how the application of regression models could foster comparisons between studies with different exposure concentrations and time frames (see below).…”

“…Cluster "Trae" contains >20 genes coding for crystallin protein subunits that are important for lens development in ZFE, which happens between 16 and 96 hpf [80, 81]. Those transcripts were found to be commonly down-regulated in response to various chemical exposures in earlier studies [18, 82], as well. Cluster "John" is down-regulated at 72 hpe and contains genes coding for different proteolytic enzymes of the pancreas.…”

“…Furthermore, comparability between toxicogenomic datasets is typically limited owing to substantial differences in study designs, e.g. with respect to selected exposure time and concentration [18]. In their pioneering studies investigating toxicogenomic fingerprints Hamadeh et al [9] and Yang et al [10] showed that responses vary with exposure time and concentration.…”

Pesticides diazinon and diuron increase glutathione levels and affect multixenobiotic resistance activity and biomarker responses in zebrafish (Danio rerio) embryos and larvae

“…Hence, they have become an important tool in assessing the modes of action and effects of various xenobiotics [4,5]. Not only have they been used for the assessment of toxicant effects on embryonic development [6], but they have also been utilized to analyze changes in behavior (e.g., [7][8][9][10]), altered enzyme activities [4,11], as well as changes on a gene expression level [5,[11][12][13][14] and oxidative stress induction [15], providing valuable data for the risk assessment of xenobiotics and their potential adverse effects on the aquatic environment.…”

Strengthen the European collaborative environmental research to meet European policy goals for achieving a sustainable, non-toxic environment

“…This may be illustrated by the monitoring of toxic stressors in European water bodies as performed in SOLUTIONS. Starting with the collation and investigation of modes of action and toxicogenomics of known water contaminants [38,39], an effect-based monitoring strategy and the corresponding toolbox [24] were developed, rigorously evaluated and adapted using selected chemicals [40], mixtures [41] and field samples [42]. Through extensive stakeholder dialogue, policy-related working groups, workshops, via scientific and popular publications plus close collaboration with relevant science-policy interaction networks such as NORMAN, the new concepts were discussed, refined and integrated in the decision-making processes regarding the review of WFD [43].…”