Danio rerio
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA248661 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally-dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at a concentration that induces developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burden was analyzed at these time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the smallest number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure and may provide a path for unraveling the toxicity of complex PAH mixtures. Gene expression was measured in zebrafish embryos after exposure to PAHs. Embryos were batch-exposed in groups of 40 to 25 μM BAA, 25 μM DBT, 25 μM PYR or 1% DMSO vehicle control starting at 6 hpf and collected at 24 or 48 hpf. Four independent biological replicates were prepared for each treatment. The reference was a pool of zebrafish embryos exposed to DMSO control until 24 and 48 hpf.
2013-05-15 | E-GEOD-44130 | biostudies-arrayexpress
Project description:Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally-dependent manner, and induce toxicity via both AHR-dependent and -independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at a concentration that induces developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burden was analyzed at these time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the smallest number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure and may provide a path for unraveling the toxicity of complex PAH mixtures.
2013-05-15 | GSE44130 | GEO
Project description:The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor well known for mediating the toxicity of environmental chemicals such as polychlorinated biphenyls (PCBs) and polyaromatic hydrocarbons (PAHs). There is extensive knowledge on the range of target genes regulated by AHR ligands. However, there is limited information on the effect of AHR ligands on DNA methylation. The objective of this study is to investigate genome-wide changes in DNA methylation and gene expression patterns in response to PCB126 exposure. Adult zebrafish were exposed to 10 nM PCB126 for 24 hours (waterborne exposure) and were reared in clean water for 7 days before tissue sampling. DNA methylation and transcriptional changes in the liver and brain tissues were quantified by Reduced Representation Bisulfite Sequencing (RRBS) and RNAseq, respectively. RRBS analysis revealed DNA hypomethylation in response to PCB exposure in both liver and brain tissues. We observed 482 and 476 differentially methylated regions (DMRs) in the liver and brain tissues respectively. Most of the DMRs are located more than 20 kilobases upstream of the transcriptional start sites. RNAseq results from the liver revealed differential expression of genes related to xenobiotic metabolism, oxidative stress and carbohydrate metabolism in response to PCB exposure. In the brain, PCB exposure altered the expression of genes involved in myelination and glutamate signaling. Our results suggest that there is very little correlation between DNA methylation and gene expression patterns among the differentially expressed genes (DEGs). We are currently investigating the relationship between DMRs and DEGs.
2017-09-30 | GSE104221 | GEO
Project description:DNA Damage Response Is Involved in the Developmental Toxicity of Mebendazole in Zebrafish Retina
| PRJNA302889 | ENA
Project description:Analysis of MicroRNA Expression in Embryonic Developmental Toxicity Induced by microcystin arginine arginine (MC-RR).
| PRJNA140127 | ENA
Project description:Dioxin and dioxin-related polychlorinated biphenyls are potent toxicants with association with developmental heart defects and congenital heart diseases. However, the underlying mechanism of their developmental toxicity is not fully understood. Further, different animals show distinct susceptibility and phenotypes after exposure, suggesting possible species-specific effects. Using a human embryonic stem cell (ESC) cardiomyocyte differentiation model, we examined the impact, susceptible window, and dosage of 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD) on human cardiac development. We showed that treatment of human ESCs with TCDD at the ESC stage inhibits cardiomyocyte differentiation, and the effect is largely mediated by the aryl hydrocarbon receptor (AHR). We further identified genes that are differentially expressed after TCDD treatment by RNA-sequencing, and genomic regions that are occupied by AHR by chromatin immunoprecipitation and high-throughput sequencing. Our results support the model that TCDD impairs human ESC cardiac differentiation by promoting AHR binding and repression of key mesoderm genes. More importantly, our study demonstrates the toxicity of dioxin in human embryonic development and uncovered a novel mechanism by which dioxin and AHR regulates lineage commitment. It also illustrates the power of ESC-based models in the systematic study of developmental toxicology.
2018-10-31 | GSE122001 | GEO
Project description:Polycyclic Aromatic Hydrocarbons (PAHs) are diverse environmental pollutants associated with adverse human health effects. Many studies focus on the carcinogenic effects of a limited number of PAHs and there is an increasing need to understand mechanisms of developmental toxicity of more varied yet environmentally relevant PAHs. A previous study characterized the developmental toxicity of 123 PAHs in zebrafish. Based on phenotypic responses ranging from complete inactivity to acute mortality, we classified these PAHs into eight bins, selected 16 representative PAHs, and exposed developing zebrafish to the concentration of each PAH that induced 80% phenotypic effect. We conducted RNA sequencing at 48 h post fertilization to identify gene expression changes as a result of PAH exposure.
2020-08-22 | GSE156656 | GEO
Project description:Background: A structurally diverse group of chemicals, including polycyclic aromatic hydrocarbons (PAHs), can inappropriately activate the aryl hydrocarbon receptor (AHR) and lead to adverse health effects. In the zebrafish model, repression of sox9b has a causal role in several AHR-mediated toxic responses, including craniofacial cartilage malformations; however, the mechanism of sox9b repression remains unknown. We previously identified a long non-coding RNA, slincR, which is increased (in an AHR-dependent manner) by multiple AHR ligands and is required for the AHR-activated repression of sox9b. Objective: Enhance our understanding of the signaling events downstream of AHR activation that contribute to toxic responses. To understand slincR’s role in the TCDD-induced toxicity pathway, we performed RNA-sequencing and gene ontology enrichment analysis on 48 hpf control and slincR morphants exposed to 0.1% DMSO or 1 ng/mL TCDD.
2018-10-25 | GSE106131 | GEO
Project description:Effect of waterborne exposure to carcinogenic PAHs on adult zebrafish hepatic transcriptome
| PRJNA187042 | ENA
Project description:Dioxin and dioxin-related polychlorinated biphenyls are potent toxicants with association with developmental heart defects and congenital heart diseases. However, the underlying mechanism of their developmental toxicity is not fully understood. Further, different animals show distinct susceptibility and phenotypes after exposure, suggesting possible species-specific effects. Using a human embryonic stem cell (ESC) cardiomyocyte differentiation model, we examined the impact, susceptible window, and dosage of 2,3,7,8‑tetrachlorodibenzo‑p‑dioxin (TCDD) on human cardiac development. We showed that treatment of human ESCs with TCDD at the ESC stage inhibits cardiomyocyte differentiation, and the effect is largely mediated by the aryl hydrocarbon receptor (AHR). We further identified genes that are differentially expressed after TCDD treatment by RNA-sequencing, and genomic regions that are occupied by AHR by chromatin immunoprecipitation and high-throughput sequencing. Our results support the model that TCDD impairs human ESC cardiac differentiation by promoting AHR binding and repression of key mesoderm genes. More importantly, our study demonstrates the toxicity of dioxin in human embryonic development and uncovered a novel mechanism by which dioxin and AHR regulates lineage commitment. It also illustrates the power of ESC-based models in the systematic study of developmental toxicology.
2018-10-31 | GSE122002 | GEO