Danio rerio
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ABSTRACT:
PROVIDER: PRJNA302889 | ENA |
REPOSITORIES: ENA
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Project description:Intestinal helminths cause iron-deficiency anemia in pregnant women, associated with premature delivery, low birth weight, maternal ill health, and maternal death. Although benzimidazole compounds such as mebendazole (MBZ) are highly efficacious against helminths, there are limited data on its use during pregnancy. In this study, we performed in vivo imaging of the retinas of zebrafish larvae exposed to MBZ, and found that exposure to MBZ during 2 and 3 days post-fertilization caused malformation of the retinal layers. To identify the molecular mechanism underlying the developmental toxicity of MBZ, we performed transcriptome analysis of zebrafish eyes. The analysis revealed that the DNA damage response was involved in the developmental toxicity of MBZ. We were also able to demonstrate that inhibition of ATM significantly attenuated the apoptosis induced by MBZ in the zebrafish retina. These results suggest that MBZ causes developmental toxicity in the zebrafish retina at least partly by activating the DNA damage response, including ATM signaling, providing a potential adverse outcome pathway in the developmental toxicity of MBZ in mammals.
2016-03-24 | GSE75245 | GEO
Project description:Methylmercury (MeHg) is a ubiquitous environmental toxicant that is often detected in the tissues of fish-eating species. It has been well established that prenatal exposure to MeHg can lead to widespread brain damage and impaired neurological development resulting in defects ranging from severe cerebral palsy and cognitive deficits to impaired motor and sensory function. A wide range of environmental toxicants have been shown to induce transgenerational inheritance of diseases via changes in DNA methylation—a well-known epigenetic modification. Our previous research has demonstrated that developmental MeHg exposure may yield transgenerational inheritance of neurological dysfunction in adult F3-lineage zebrafish via quantitative neurobehavioral assays that evaluated the visual startle response, retinal electrophysiology, and locomotor function. The objective of the current study was to examine the correlation between neurobehavioral phenotypes and the transcriptome activity in the brain and retina of F3 zebrafish by RNA sequencing (RNAseq). Transcriptomic analyses of F3 generation MeHg-treated zebrafish (compared to control) revealed significant gene dysregulation in both the brain and retina. There were 1648 and 138 differentially expressed genes in the retina and brain, respectively (FDR <0.05). Thirty-five genes were commonly dysregulated in both organs. Gene set enrichment analysis revealed significantly enriched pathways including: neurodevelopment, visual functions, phototransduction, and motor movement. Moreover, commonly dysregulated genes were associated with circadian rhythm and metabolic pathways, as well as arginine and proline metabolism. To our knowledge, this is the first evidence of a transgenerational transcriptome induced by ancestral developmental exposure to MeHg in any species. If the transgenerational phenotypes, transcriptome, homologous biomarkers, or similar molecular pathways hold true for human populations, our findings have significant impact on global public health in terms of identifying the susceptible populations using biomarkers and preventing transgenerational inheritance of MeHg-induced neurobehavioral deficits.
2018-01-01 | GSE73795 | GEO
Project description:Methylmercury (MeHg) is a ubiquitous environmental toxicant that is often detected in the tissues of fish-eating species. It has been well established that prenatal exposure to MeHg can lead to widespread brain damage and impaired neurological development resulting in defects ranging from severe cerebral palsy and cognitive deficits to impaired motor and sensory function. A wide range of environmental toxicants have been shown to induce transgenerational inheritance of diseases via changes in DNA methylation—a well-known epigenetic modification. Our previous research has demonstrated that developmental MeHg exposure may yield transgenerational inheritance of neurological dysfunction in adult F3-lineage zebrafish via quantitative neurobehavioral assays that evaluated the visual startle response, retinal electrophysiology, and locomotor function. The objective of the current study was to examine the correlation between neurobehavioral phenotypes and the transcriptome activity in the brain and retina of F3 zebrafish by RNA sequencing (RNAseq). Transcriptomic analyses of F3 generation MeHg-treated zebrafish (compared to control) revealed significant gene dysregulation in both the brain and retina. There were 1648 and 138 differentially expressed genes in the retina and brain, respectively (FDR <0.05). Thirty-five genes were commonly dysregulated in both organs. Gene set enrichment analysis revealed significantly enriched pathways including: neurodevelopment, visual functions, phototransduction, and motor movement. Moreover, commonly dysregulated genes were associated with circadian rhythm and metabolic pathways, as well as arginine and proline metabolism. To our knowledge, this is the first evidence of a transgenerational transcriptome induced by ancestral developmental exposure to MeHg in any species. If the transgenerational phenotypes, transcriptome, homologous biomarkers, or similar molecular pathways hold true for human populations, our findings have significant impact on global public health in terms of identifying the susceptible populations using biomarkers and preventing transgenerational inheritance of MeHg-induced neurobehavioral deficits.
2018-01-01 | GSE73794 | GEO
Project description:Genome-scale DNA methylation maps of Zebrafish Muller glia during retina regeneration
| PRJNA218577 | ENA
Project description:Humans and animals have problems producing eggs with high embryo developmental competence, but the causes of poor egg quality are usually unknown. This study delivered the first proteomic portraits of egg quality in zebrafish, a leading model for vertebrate development. Egg batches of good and poor quality, evidenced by embryo survival for 24 h, were used to create pooled or replicated sample sets subjected to different levels of fractionation before LC-MS/MS. Obtained spectra were searched against a custom zebrafish proteome database and detected proteins were annotated, categorized and quantified based on their normalized spectral counts. Manual and automated enrichment analyses were highly confirmative, showing that good and poor quality eggs have disparate proteomes. Proteins involved in protein synthesis, energy metabolism, and lipid metabolism, and certain vitellogenin products were strikingly underrepresented in poor quality eggs. Poor quality eggs also had significantly higher representation of proteins related to immune system and endosome/lysosome functioning, oncogenes, and apoptosis, as well as lectins and egg envelope proteins. Quantitative comparisons of highly abundant proteins revealed 9 candidate egg quality markers warranting further study. In conclusion, the zebrafish egg proteome appears to be linked to embryo developmental potential, a phenomenon that begs further investigation.
2017-11-27 | PXD005137 | Pride
Project description:Humans and animals have problems producing eggs with high embryo developmental competence, but the causes of poor egg quality are usually unknown. This study delivered the first proteomic portraits of egg quality in zebrafish, a leading model for vertebrate development. Egg batches of good and poor quality, evidenced by embryo survival for 24 h, were used to create pooled or replicated sample sets subjected to different levels of fractionation before LC-MS/MS. Obtained spectra were searched against a custom zebrafish proteome database and detected proteins were annotated, categorized and quantified based on their normalized spectral counts. Manual and automated enrichment analyses were highly confirmative, showing that good and poor quality eggs have disparate proteomes. Proteins involved in protein synthesis, energy metabolism, and lipid metabolism, and certain vitellogenin products were strikingly underrepresented in poor quality eggs. Poor quality eggs also had significantly higher representation of proteins related to immune system and endosome/lysosome functioning, oncogenes, and apoptosis, as well as lectins and egg envelope proteins. Quantitative comparisons of highly abundant proteins revealed 9 candidate egg quality markers warranting further study. In conclusion, the zebrafish egg proteome appears to be linked to embryo developmental potential, a phenomenon that begs further investigation.
2017-11-27 | PXD005129 | Pride
Project description:To identify molecular effects of the antineoplastic agent PKC412 (Midostaurin), we applied gene expression profiling in zebrafish using whole genome microarrays. Zebrafish eleuthero-embryos were exposed for 6 dpf to nominal levels of 2 μg/L and 40 μg/L PKC412. Among the 259 and 511 altered transcripts at both concentrations, respectively, the expressions of genes involved in the circadian rhythm were of interest. Alteration of swimming behaviour was not noted. Pathways of interest affected by PKC412 were angiogenesis, apoptosis, DNA damage response and response to oxidative stress. Angiogenesis was not altered by PKC412 treatment at both concentrations. Apoptosis occurred in olfactory placodes of embryos exposed to 40 μg/L, and DNA damage was induced at both PKC412 concentrations. However, there were no significant effects on reactive oxygen species formation. This study leads to the conclusion that PKC412-induced alterations of gene transcripts are partly paralleled by physiological effects at high, but not at low PKC412 concentrations expected to be of environmental relevance. Gene expression in zebrafish eleuthero-embryos was measured after exposure for 6dpf to 2 ug/L and 40 ug/L PKC412 or to the respective controls. A total of 12 arrays (Agilent 4 × 44 K Zebrafish microarray) were used, including four for the water control group, four for the solvent control group, four for the 2 μg/L and four for the 40 μg/L PKC412 dose group.
2011-07-22 | E-GEOD-23156 | biostudies-arrayexpress
Project description:To identify molecular effects of the antineoplastic agent PKC412 (Midostaurin), we applied gene expression profiling in zebrafish using whole genome microarrays. Zebrafish eleuthero-embryos were exposed for 6 dpf to nominal levels of 2 μg/L and 40 μg/L PKC412. Among the 259 and 511 altered transcripts at both concentrations, respectively, the expressions of genes involved in the circadian rhythm were of interest. Alteration of swimming behaviour was not noted. Pathways of interest affected by PKC412 were angiogenesis, apoptosis, DNA damage response and response to oxidative stress. Angiogenesis was not altered by PKC412 treatment at both concentrations. Apoptosis occurred in olfactory placodes of embryos exposed to 40 μg/L, and DNA damage was induced at both PKC412 concentrations. However, there were no significant effects on reactive oxygen species formation. This study leads to the conclusion that PKC412-induced alterations of gene transcripts are partly paralleled by physiological effects at high, but not at low PKC412 concentrations expected to be of environmental relevance.
2011-07-23 | GSE23156 | GEO