Toxicogenomic signatures associated with methylmercury induced developmental toxicity in the zebrafish embryos.
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA851283 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19761446_1.fastq.gz | Fastqsanger.gz | |||
| SRR19761446_2.fastq.gz | Fastqsanger.gz | |||
| SRR19761447_1.fastq.gz | Fastqsanger.gz | |||
| SRR19761447_2.fastq.gz | Fastqsanger.gz | |||
| SRR19761448_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Methylmercury (MeHg) is a teratogen with adverse effects on embryogenesis from fish to man. The adverse developmental outcomes of MeHg are well understood, but molecular understanding of teratogenic effects is rather limited. We performed here a genome - wide transcriptional analyses of 6, 30 and 50 μg/L MeHg treated zebrafish embryos from 4 to 72 h post-fertilization (hpf) using RNA-sequencing and self-printed microarray, and conducted a systematical comparison of MeHg - induced transcriptomic responses observed in this and our previous studies. We found that genes linked to gene ontology in terms of oxidative stress, visual, photoreception and cilium, and GABAergic synapse were enriched in embryo exposed from 4 to 72 hpf. The significantly altered genes involved in MAP kinase, TGF beta signaling pathway, oxidative phosphorylation, and glutathione metabolism were enriched across different exposure scenarios. We obtain 22 genes significantly regulated by MeHg, particularly the significant changes were determined in embryos exposed to 6 μg/L MeHg, which did not cause obviously teratogenic effects. Our findings show that the genes whose expression is altered by MeHg in embryonic stages may play important roles in adverse developmental endpoints and might be served as signatures for teratogenic effects.
2022-12-21 | GSE206531 | GEO
Project description:Dextromethorphan is widely used in over-the-counter cough and cold medications. Its efficacy and safety for infants and young children remains to be clarified. The present study was designed to use zebrafish as a model to investigate the potential toxicity of dextromethorphan during embryonic and larval development. Three sets of zebrafish embryos/larvae were exposed to dextromethorphan at 24, 48 and 72 h post fertilization (hpf), respectively, during the embryonic/larval development. Compared with the 48 and 72 hpf exposure sets, the embryos/larvae in the 24 hpf exposure set showed much higher mortality rates which increased in a dose-dependent manner. Bradycardia and reduced blood flow were observed for the embryos/larvae treated with increasing concentrations of dextromethorphan. Morphological effects of dextromethorphan exposure, including yolk sac and cardiac edema, craniofacial malformation, lordosis, non-inflated swim bladder and missing gill, were also more frequent and severe among zebrafish embryos/larvae exposed to dextromethorphan at 24 hpf. Whether the more frequent and severe developmental toxicity of dextromethorphan observed among the embryos/larvae in the 24 hpf exposure set, as compared with the 48 and 72 hpf exposure sets, is due to the developmental expression of the phase I and phase II enzymes involved in the metabolism of dextromethorphan remains to be clarified. A reverse transcription-polymerase chain reaction analysis, nevertheless, revealed developmental stage-dependent expression of mRNAs encoding SULT3 ST1 and SULT3 ST3, two enzymes previously shown to be capable of sulfating dextrorphan, an active metabolite of dextromethorphan.
| S-EPMC3515875 | biostudies-literature
Project description:Tanshinone IIA (Tan-IIA) is derived from the dried roots of Salvia miltiorrhiza Bunge, a traditional Chinese medicine. Although Salvia miltiorrhiza has been applied for many years, the toxicity of the mono-constituent of Salvia miltiorrhiza, tanshinone IIA, is still understudied. This study evaluated the cardiotoxicity and developmental malformations of Tan-IIA by using zebrafish normal embryos and dechorionated embryos. After treatment with Tan-IIA in different concentrations for four-day periods, obvious pericardial edema, spinal curvature, and even missing tails were observed in zebrafish embryos. The LC50 values in the dechorionated embryo group at 72 h post-fertilization (hpf) and 96 hpf were 18.5 μM and 12.8 μM, respectively, and the teratogenicity was manifested at a concentration of about 1 µM. The main endpoints of teratogenicity were scoliosis, malformation of tail, and pericardium edema. Our findings displayed the potential cardiotoxicity and severe impact on the abnormal development of Tan-IIA in zebrafish embryo at high concentrations, which may help avoid the risk of its clinical application.
| S-EPMC6154573 | biostudies-literature
Project description:Methylmercury (MeHg) toxicity in humans manifests deficits in neurological function. Cases of prenatal exposure to mercury have established that the developing nervous system is most highly susceptible to perturbation by MeHg. At a cellular level, MeHg-induced defects result from altered neuronal proliferation, migration and pathfinding. However, the molecular targets of MeHg that give rise to these outcomes are not fully understood. In an overall effort to identify the fundamental molecular targets of MeHg in neural development, we are investigating the effects of MeHg on gene expression and protein function in the Drosophila model. Since the fundamental signaling pathways in development of multicellular animals have been extensively characterized in Drosophila, and demonstrate high degree of conservation in vertebrates, we believe these data will lead us to the most pertinent pathways affected by MeHg and begin to elucidate the mechanism of MeHg neural toxicity relevant to cases of human exposure to this prevalent environmental toxin. Our aim is to identify fundamental signaling pathways in neural development that are targets for MeHg poisoning. Our hypothesis is that MeHg, by direct interaction with cysteine thiol groups, alters the function signaling pathway proteins and subsequently alters transcription of target genes in the respective pathways. Our hypothesis is supported by our recent data demonstrating a direct action of MeHg in activating the Notch receptor pathway and upregulating target gene expression. We anticipate a microarray analysis will elucidate additional fundamental signaling pathways where transcription is affected by this toxin. Fertilized female flies are fed on food containing methylmercury (1-20 micromolar) or solvent control (DMSO) for a period of five days to allow for MeHg penetration in to eggs. Flies are then transfered to a cage for embryo collection for a discrete window of time (e.g. 1hr). Embryos are aged 16-24 hours and collected for total RNA extraction using the Trizol reagent. Total RNA is quantitated by spectrophotometry with a Nanodrop reader. While concentration dependent effects of MeHg are of interest, initial experiments will be conducted on samples exposed to a single concetration known to illicit effect in other bioassays (e.g. 10 micromolar). The goal is to see which genes are up- or down-regulated with MeHg exposure, as compared to control embryos that are not exposed. Emphasis in the analysis stage will be in identifying target genes of known signaling pathways.
2008-03-13 | E-GEOD-9271 | biostudies-arrayexpress
Project description:General anesthetics can cause neurological damage and long-term behavioral/cognitive impairment during fetal and early postnatal life. However, the adverse influence on embryo development induced by propofol is unclear. We used embryonic zebrafish to explore the effects of propofol on embryonic and larval growth and development, and the related apoptotic mechanism. Zebrafish embryos were immersed in propofol (1, 2, 3, 4, and 5 μg/ml) dissolved in E3 medium from 6 to 48 hours post fertilization (hpf). The survival rate, locomotion, heart rate, hatchability, deformity rate, and body length were analyzed at defined stages. Terminal deoxynucleotidyl transferase nick-end-labeling was used to detect zebrafish embryo apoptosis, and the expression levels of apoptosis-related genes were determined using quantitative real-time reverse transcription PCR and whole-mount in situ hybridization. Larvae at 48 hpf were anesthetized by immersion in E3 culture medium containing 2 μg/ml propofol, the reasonable anesthetic concentration for zebrafish embryos, which caused significant caudal fin dysplasia, light pigmentation, edema, hemorrhage, and spinal deformity, and decreased the hatchability, body length, and heart rate. The numbers of apoptotic cells in propofol-treated 12, 48 and 72 hpf embryos increased significantly, and the mRNA expression levels of intrinsic apoptosis pathway-related casp3a, casp3b, casp9, and baxb genes were upregulated, mainly in the head and tail. Propofol decreased apoptosis in the head and back of 24 hpf zebrafish, which was consistent with the mRNA expression analysis. Our findings demonstrated that zebrafish embryos and larvae exposed to propofol experienced developmental toxicity, which correlated with the intrinsic apoptosis pathway with casp3a, casp3b, casp9, and baxb as the key genes.
| S-EPMC10228783 | biostudies-literature
Project description:Carpesii Fructus, the dried fruit of Carpesium abrotanoides L., has been used as a traditional Chinese medicine for centuries to kill intestinal parasites in children. It has been recorded as a mildly toxic medicine in the Chinese pharmacopoeia. However, little proof of its toxicology has been reported in modern pharmacology. This study investigated for the first time its developmental toxicity on zebrafish embryos/larvae from 6 to 96 h post-fertilization (hpf). In addition, the enzymes and genes associated with oxidative stress and apoptosis were tested to investigate the potential toxicologic mechanism preliminarily. The observation of toxicologic endpoints showed the developmental toxicity of Carpesii Fructus. Pericardial edema, yolk sac edema, bleeding tendency, and enlarged yolk were the most commonly occurring morphological changes observed in our study. According to the results of acridine orange staining and morphological observation, the developing heart was speculated to be the target organ of toxicity. Furthermore, Carpesii Fructus exposure changed the activities of defense enzymes, increased malondialdehyde (MDA) content, decreased caspase-3 activity, and altered mRNA levels of related genes (ogg1, p53, Cu/Zn-Sod, Mn-Sod, and Cat↓; Gpx↑) in zebrafish larvae, indicating that oxidative stress and additional apoptosis should have roles in the developmental toxicity of Carpesii Fructus. This is the first study that provides proof of modern pharmacology on the teratogenicity and possible toxicologic mechanism of Carpesii Fructus.
| S-EPMC6062322 | biostudies-literature
Project description:Methylmercury (MeHg) is a developmental neurotoxicant and teratogen and is hypothesized to perturb a wide range of biological processes, like other metals including arsenic (As) and cadmium (Cd). Common inbred mouse strains including C57 (sensitive) and SWV (resistant) display differences in sensitivity to metals such as As and Cd when exposed during neurulation. In this study, we investigated the impact of MeHg on neurulation, assessing for potential differences in sensitivity and associated toxicogenomic response in C57 and SWV mouse embryos. Parallel with morphological assessments of neural tube closure, we evaluated quantitative differences in MeHg-induced alterations in expression between strains at the gene level and within gene-enriched biological processes. Specifically, we observed differing sensitivities to MeHg-induced impacts on neural tube closure between C57 and SWV embryos in a time-dependent manner. These observations correlated with greater impact on the expression of genes associated with development and environmental stress-related pathways in the C57 compared to the SWV. Additional developmental parameters (e.g. mortality, growth effects) evaluated showed mixed significant effects across the two strains and did not support observations of differential sensitivity to MeHg. This study provides potential insights into MeHg-induced mechanisms of developmental toxicity, alterations associated with increased MeHg sensitivity and common biological processes affected by metals in embryos undergoing neurulation.
| S-EPMC2924281 | biostudies-literature
Project description:Lurasidone Induces Developmental Toxicity and Behavioral Impairments in Zebrafish Embryos
| PRJNA1277809 | ENA
Project description:Carbendazim (CAR) and enrofloxacin (ENF) are frequently detected in fruits and meat products, respectively. Since most people consume fruits, vegetables, and meat products, combined exposure is possible, necessitating further evaluation of toxic interactions. In this study, the developmental toxicity of separate and combined exposure was examined in zebrafish embryos. Carbendazim exposure at 0.79 mg/L and above significantly affected developmental parameters, while enrofloxacin alone had no substantial effects on these developmental parameters within the selected concentration range (0.10-0.40 mg/L). Surprisingly, ENF antagonized the CAR-evoked reduction in the 48 hpf (hours post-fertilization) hatching rate and the increases in the 96 hpf malformation and lethality rates. The results revealed that the antagonism might be associated with reciprocal effects of these compounds on metabolism-related genes, such as cyp7a1 and apoa1a. These results reveal a complex interaction between ENF and CAR on metabolic regulation during development and highlight the importance of combined assessment for agents with the potential for simultaneous exposure.
| S-EPMC8704853 | biostudies-literature
Project description:As part of the West Virginia Chemical Spill research program, NTP evaluated three chemicals that were spilled into the Elk Rever in West Virginia for their ability to cause toxicity or biological changes in a short-term toxicogenomic study
2018-10-15 | GSE119833 | GEO