Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of liver from wild type and ESR1 mutant mice (EAAE/EAAE) after treatment with ethinylestradiol versus vehicle

ABSTRACT: To understand the contribution of direct versus indirect DNA binding of estrogen-activated ERa and ERa(EAAE/EAAE) on gene expression in the murine liver, RNA was isolated from the liver of wild-type and ERa(EAAE/EAAE) mice treated perorally with 100µg/kg ethinylestradiol(EE) or vehicle for 4 or 24 hours.

ORGANISM(S): Mus musculus

SUBMITTER: Henrik Seidel

PROVIDER: E-TABM-739 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

DNA binding by estrogen receptor-alpha is essential for the transcriptional response to estrogen in the liver and the uterus.

Ahlbory-Dieker Dörthe L DL Stride Brenda D BD Leder Gabriele G Schkoldow Jenny J Trölenberg Susanne S Seidel Henrik H Otto Christiane C Sommer Anette A Parker Malcolm G MG Schütz Günther G Wintermantel Tim M TM

Molecular endocrinology (Baltimore, Md.) 20090702 10

The majority of the biological effects of estrogens in the reproductive tract are mediated by estrogen receptor (ER)alpha, which regulates transcription by several mechanisms. Because the tissue-specific effects of some ERalpha ligands may be caused by tissue-specific transcriptional mechanisms of ERalpha, we aimed to identify the contribution of DNA recognition to these mechanisms in two clinically important target organs, namely uterus and liver. We used a genetic mouse model that dissects DNA ...[more]

PMID: 19574448

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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 mRNA expression profiling experiment 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 ethinylestradiol as model substances for estrogenic perturbation in a modified zebrafish embryo toxicity test (zFET). These signatures allow for the identification of gene expression changes and the 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). In a modified version of the zebrafish embryo toxicity test (OECD 236), 15 fertilized eggs were exposed to two different sub lethal concentrations of ethinylestradiol for 96 hours under semi-static conditions. Each test comprised of a low exposure (LE, 20 µg/L) and high exposure (HE, 200 µg/L) and negative control (NC) group and was performed in triplicates. At 96 hours post fertilization (hpf), 10 larvae were randomly picked for each sample and pooled for RNA and protein extraction with NucleoSpin RNA/Protein kit (Macherey-Nagel). RNA quality was assessed with a 2100 Bioanalyzer system (Agilent) before coding RNA was purified (PolyA selection with TruSeq RNA Library Prep Kit v2) and sequenced on an Illumina HiSeq 4000 System (Illumina) in 50 bp single read mode, producing roughly 30 million reads per sample. Adapter sequences were removed with trimmomatic and sequences were aligned to the D.rerio reference genome GRCz11 with STAR. Counting of feature mapped reads was performed through featureCounts. Library gene count tables were then merged to a single count matrix as input for differential gene expression analysis with DESeq2.

Dataset Information

Transcription profiling of liver from wild type and ESR1 mutant mice (EAAE/EAAE) after treatment with ethinylestradiol versus vehicle

Publications

DNA binding by estrogen receptor-alpha is essential for the transcriptional response to estrogen in the liver and the uterus.

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