Effects of anti-androgenic compounds on zebrafish insulin mutants
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB30451 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3011942.fastq.gz | Fastqsanger.gz | |||
| ERR3011943.fastq.gz | Fastqsanger.gz | |||
| ERR3011944.fastq.gz | Fastqsanger.gz | |||
| ERR3011945.fastq.gz | Fastqsanger.gz | |||
| ERR3011946.fastq.gz | Fastqsanger.gz |
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Project description:Aiming to identify insulin-independent modulators of glucose homeostasis, we performed a drug screen on zebrafish insulin (ins) mutants and identified androgen receptor (AR) antagonists. To investigate how AR antagonism mediates glucose level reduction in ins mutants, we evaluated the effects of antagonist treatment using transcriptomic studies. RNA-Seq analyses were performed on 120 hours post fertilization (hpf) ins mutants treated with Flutamide or Cyproterone starting at 84 hpf compared to vehicle (DMSO) treated mutants.
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Project description:Endocrine disruption (ED) can trigger far-reaching effects on environmental populations, justifying a refusal of market approval for chemicals with ED properties. For the assessment of ED effects on development and reproduction, regulatory decisions mostly rely on apical endpoints from in vivo testing with adult animals. Here, we present a rapid and reproducible data dependent proteomics approach for identifying comprehensive molecular fingerprints interfering with the sexual endocrine system in zebrafish (Danio rerio) embryos as an alternative to animal testing. For this, we have analysed methyltestosterone as model substances for androgenic perturbation in a modified zebrafish embryo toxicity test (zFET). These signatures allow for a definition of solid biomarkers as tools in screening approaches and for integration in chronic toxicity studies for identifying suspect ED substances, in the fish early life-stage test (OECD TG 210).
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Project description:To discover insulin-independent pathways controlling glucose homeostasis, we generated zebrafish insulin mutants. Aiming to characterize the transcriptional changes induced by deletion of insulin, we performed a microarray analysis comparing insulin mutant animals with their non-mutant siblings at 108 hours post fertilization. Embryos were grown at 28 degrees C until 108 hpf, and were separately collected as mutants or non-mutants to form pools of 10 animals per sample. Total RNA was isolated, sample quality was tested using a Bioanalyzer and microarray analysis was performed by Oak Labs (Germany)
2018-10-20 | E-MTAB-7282 | biostudies-arrayexpress
Project description:The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable endocrine disruption (ED) assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17a-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos.
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Project description:The identification of endocrine disruptive properties of chemicals certain to enter the aquatic environment relies on toxicity tests with fish, assessing adverse effects on reproduction and sexual development. The demand for quick, reliable endocrine disruption (ED) assays favored the use of fish embryos as alternative test organisms. We investigated the application of a transcriptomics-based assay for estrogenic and anti-androgenic chemicals with zebrafish embryos. Two reference compounds, 17a-ethinylestradiol and flutamide, were tested to evaluate the effects on development and the transcriptome after 48h-exposures. Comparison of the transcriptome response with other estrogenic and anti-androgenic compounds (genistein, bisphenol A, methylparaben, linuron, prochloraz, propanil) showed commonalities and differences in regulated pathways, enabling us to classify the estrogenic and anti-androgenic potencies. This demonstrates that different mechanism of ED can be assessed already in fish embryos. Newly fertilized embryos (<2hpf) were exposed for 48 hours to 0.65mg/l (EC10) and 0.8mg/l (EC20) 17-alpha ethinylestradiol (EE2), 1.2mg/l (EC10) and 1.4mg/l (EC20) flutamide, 8 mg/l (EC10)and 8.5mg/l (EC20) bisphenol A(BPA), 0.8 mg/l (EC10) and 1.1mg/l (EC20) propanil, 19.8mg/l (EC10) and 24.4mg/l (EC20) methylparaben, 1.2 mg/l (EC10) and 1.3mg/l (EC20) linuron as well as to 1.7mg/l (EC10) and 2 mg/l (EC20) prochloraz. Water controls were included in all studies and acetone solvent controls were applied when indicated (AC). For each study, four replicates (a,b,c,d) were performed per condition, each consisting of 24 pooled embryos.
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