Effects of haloperidol on zebrafish and fathead minnow gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Pimephales promelas
SUBMITTER: Dan Villeneuve
PROVIDER: E-GEOD-15216 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Publications
II: Effects of a dopamine receptor antagonist on fathead minnow dominance behavior and ovarian gene expression in the fathead minnow and zebrafish.
Villeneuve Daniel L DL Garcia-Reyero Natàlia N Martinović Dalma D Mueller Nathaniel D ND Cavallin Jenna E JE Durhan Elizabeth J EJ Makynen Elizabeth A EA Jensen Kathleen M KM Kahl Michael D MD Blake Lindsey S LS Perkins Edward J EJ Ankley Gerald T GT
Ecotoxicology and environmental safety 20091107 4
Neurotransmitters such as dopamine play an important role in reproductive behaviors and signaling. Neuroendocrine-active chemicals in the environment have potential to interfere with and/or alter these processes. A companion study with the dopamine 2 receptor antagonist, haloperidol, found no evidence of a direct effect of the chemical on fish reproduction. This study considered haloperidol's potential effects on behavior and ovarian gene expression. Male fathead minnows exposed to 50 microg hal ...[more]
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Project description:This experiment was conducted as part of an overall study aimed at examining effects of a dopamine receptor antagonist on reproduction, behavior, and gene expression in cyprinid fish. Relative to gene expression, we hypothesized that if haloperidol disrupted normal regulation of the HPG axis, there may be robust transcriptional alterations in the ovary of exposed females that might serve as useful markers of exposure and/or effects. For the purposes of this study, robust transcriptional alterations were defined as those detected in two separate fish species (fathead minnow and zebrafish), exposed to the same concentration of haloperidol for the same duration. There is a companion zebrafish microarray experiment (GSE14861) that these data are compared to. Transcriptional responses in the ovary of the two species are compared in terms of differentially expressed genes, enriched gene ontology categories they represent, and associated pathways. Fathead minnow and zebrafish microarray experiment Samples for microarray analysis were generated in a separate, 96 h, continuous flow-through experiment. Nominal treatment concentrations for the microarray experiment were 0 and 50 μg haloperidol/L. Chemical (or control water) delivery was initiated 24 h prior to adding fish to the tanks. To start the experiment, fathead minnows (4 males, 4 females per tank) were added to each of three tanks per treatment group, while zebrafish (6 males, 6 females per tank) were added to each of two tanks per group. The time of fish addition was staggered by replicate within each treatment such that all samples from a given exposure tank could be collected within 60 min of the intended 96 h exposure duration. After 96 h, male and female zebrafish and female fathead minnows were anesthetized in buffered MS-222 and weighed. Whole gonads were removed, weighed, and preserved in RNAlater. Total RNA was isolated from fathead minnow ovary samples using RNeasy kits (Qiagen). RNA quality was assessed with a Agilent 2100 Bioanalyzer and quantity was determined using a Nanodrop ND-1000 spectrophotometer (Nanodrop Technologies, Wilmington, DE, USA). Aliquots of six fathead minnow ovary RNA samples per treatment group (two from each replicate per treatment) were prepared for microarray analysis.
2010-05-16 | E-GEOD-15115 | biostudies-arrayexpress
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2011-11-21 | E-GEOD-26692 | biostudies-arrayexpress
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2011-07-01 | E-GEOD-26573 | biostudies-arrayexpress
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2011-07-01 | E-GEOD-26738 | biostudies-arrayexpress
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2010-07-06 | E-GEOD-18163 | biostudies-arrayexpress
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2010-05-15 | E-GEOD-17280 | biostudies-arrayexpress
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2008-06-14 | E-GEOD-5963 | biostudies-arrayexpress
Project description:Background; The t(12;21)(p13;q22) translocation is found in 20 to 25% of cases of childhood B-lineage acute lymphoblastic leukemia (B-ALL). This rearrangement results in the fusion of ETV6 (TEL) and RUNX1 (AML1) genes and defines a relatively uniform category, although only some patients suffer very late relapse. TEL/AML1-positive patients are thus an interesting subgroup to study, and such studies should elucidate the biological processes underlying TEL/AML1 pathogenesis. We report an analysis of gene expression in 60 children with B-lineage ALL using Agilent whole genome oligo-chips (44K-G4112A) and/or real time RT-PCR. Results; We compared the leukemia cell gene expression profiles of 16 TEL/AML1-positive ALL patients to those of 44 TEL/AML1-negative patients, whose blast cells did not contain any additional recurrent translocation. Microarray analyses of 26 samples allowed the identification of genes differentially expressed between the TEL/AML1-positive and negative ALL groups. Gene enrichment analysis defined five enriched GO categories: cell differentiation, cell proliferation, apoptosis, cell motility and response to wounding, associated with 14 genes â??RUNX1, TCFL5, TNFRSF7, CBFA2T3, CD9, SCARB1, TP53INP1, ACVR1C, PIK3C3, EGFL7, SEMA6A, CTGF, LSP1, TFPIâ?? highlighting the biology of the TEL/AML1 sub-group. These results were first confirmed by the analysis of an additional microarray data-set (7 patient samples) and second by real-time RT-PCR quantification and clustering using an independent set (27 patient samples). Over-expression of RUNX1 (AML1) was further investigated and in one third of the patients correlated with cytogenetic findings. Conclusions; Gene expression analyses of leukemia cells from 60 children with TEL/AML1-positive and -negative B-lineage ALL led to the identification of five biological processes, associated with 14 validated genes characterizing and highlighting the biology of the TEL/AML1-positive ALL sub-group. Experiment Overall Design: We carried out a prospective multicentric study on childhood B-ALL leukemia to elucidate the molecular processes involved in TEL/AML1-positive leukemia. All the patients included in this study received treatment according to the French FRALLE 2000 trial. We used Agilent whole-genome oligo-chips (44K-G4112A) to compare the gene expression signatures of TEL/AML1-positive patients to those of TEL/AML1-negative patients with no recurrent chimeric products irrespective of their clinical risk category. Previous microarray gene expression studies had revealed the effect of chromosomal alteration on transcription profiles, so we excluded from our cohort those patients with other recurrent chromosomal translocations or fusion transcripts (BCR/ABL, E2A/PBX1, MLL rearrangements). We then searched for the biological pathways associated with genes differentially expressed in TEL/AML1-positive leukemia (ETV6/RUNX1).
2008-06-16 | E-GEOD-9170 | biostudies-arrayexpress