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Microarray analysis in the zebrafish liver and telencephalon after exposure to low concentration of 17a-EE2

ABSTRACT: Experiment exposed adult male zebrafish to 10ng/L 17-alpha ethinylestradiol for three weeks. Gene expression profiling of liver and telencephalon following exposure. Keywords: estrogenic exposure

ORGANISM(S): Danio rerio

PROVIDER: GSE7220 | GEO | 2007/03/31

SECONDARY ACCESSION(S): PRJNA98291

REPOSITORIES: GEO

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Auratus goldfish genome project: Gene expression profiling in the brain of male goldfish exposed to 17α-EE2

Project description:A goldfish brain enriched cDNA combined with a carp microarray (Gracey et al., 2004). Experiment exposed adult male goldfish to 17-alpha ethinylestradiol for two weeks (two doses - 30 ng/L and 300 ng/L) Keywords: estrogenic exposure, dose response,

2006-05-31 | GSE4868 | GEO

Transcriptomal profiling of C57BL/6 wild type and ER-alpha KO mice fetal mammary gland after fetal exposure to Bisphenol A (BPA) and 17alpha-ethynylestradiol (EE2)

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Sensitive and robust gene expression changes in fish exposed to estrogen - a microarray approach

Project description:Background Vitellogenin is a well established biomarker for estrogenic exposure in fish. However, effects on gonadal differentiation at concentrations of estrogen not sufficient to give rise to a measurable vitellogenin response suggest that more sensitive biomarkers would be useful. Induction of zona pellucida genes may be more sensitive but their specificities are not as clear. The objective of this study was to find additional sensitive and robust candidate biomarkers of estrogenic exposure. Results Hepatic mRNA expression profiles were characterized in juvenile rainbow trout exposed to a measured concentration of 0.87 and 10ng ethinylestradiol/L using a salmonid cDNA microarray. The higher concentration was used to guide the subsequent identification of generally more subtle responses at the low concentration not sufficient to induce vitellogenin. A meta-analysis was performed with data from the present study and three similar microarray studies using different fish species and platforms. Within the generated list of presumably robust responses, several well-known estrogen-regulated genes were identified. Two genes, confirmed by quantitative RT-PCR (qPCR), fulfilled both the criteria of high sensitivity and robustness; the induction of the genes encoding zona pellucida protein 3 and a nucleoside diphosphate kinase (nm23). Conclusions The cross-species, cross-platform meta-analysis correctly identified several robust responses. This adds confidence to our approach used for identifying candidate biomarkers. Specifically, we propose that analyses of nm23 together with zona pellucida genes may increase the possibilities to detect an exposure to low levels of estrogenic compounds in fish.

2007-07-24 | E-MEXP-1149 | biostudies-arrayexpress

Transcriptomal profiling of C57BL/6 wild type and ER-alpha KO mice fetal mammary gland after fetal exposure to Bisphenol A (BPA) and 17alpha-ethynylestradiol (EE2)

Project description:To examine whether the BPA-induced morphological alterations of the fetal mouse mammary glands are a) associated with changes in mRNA expression reflecting estrogenic actions and/or b) dependent on the estrogen receptor α (ERα), we compared the transcriptomal effects of BPA and the steroidal estrogen ethinylestradiol (EE2) on fetal mammary tissues of wild type and ERα knock-out mice. Mammary glands from fetuses of dams exposed to vehicle, 250 ng BPA/kg BW/d or 10 ng EE2/kg BW/d from embryonic day (E) 8 were harvested at E19. Total RNA was subjected to transcriptomal profiling using Affymetrix mouse genome 430 2.0 microarray.

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Gene signaling pathways in liver of largemouth bass by a sub-chronic dietary exposure to EE2

Project description:The objective of this study was to investigate pathway signatures altered in the livers of female largemouth bass (LMB) and their potential links with biological responses by dietary exposure to 0.2 mg EE2/Kg (1% of their body weight) over two months using a transcriptomics approach. A high concentration of dietary 17alpha-ethinylestradiol (EE2) can activate key signaling pathways in response to oxidative damage may occur regardless of tumorigenesis and cancer. Female LMB received about 1.2g EE2/day/fish (from EE2-laced feed containing 0.2 mg EE2/Kg) for 60 days.

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Embryonic E14.5 telencephalon vs adult forebrain

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Development of a comprehensive toxicity pathway model for 17α-ethinylestradiol (EE2) in early life stage fathead minnows (Pimephales promelas)

Project description:The goal of this study is to characterize molecular toxicity pathways associated with ethinylestradiol-induced toxicity and link these molecular perturbations to apical outcomes of regulatory relevance.

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Project description:The mammalian telencephalon plays critical roles in cognition, motor function, and emotion. While many of the genes required for its development have been identified, the distant‐acting regulatory sequences orchestrating their in vivo expression are mostly unknown. Here we describe a digital atlas of in vivo enhancers active in subregions of the developing telencephalon. We identified over 4,600 candidate embryonic forebrain enhancers and studied the in vivo activity of 329 of these sequences in transgenic mouse embryos. We generated serial sets of histological brain sections for 145 reproducible forebrain enhancers, resulting in a publicly accessible web‐based enhancer atlas comprising over 33,000 sections. We show how this large collection of annotated telencephalon enhancers can be used to study the regulatory architecture of individual genes, to examine the sequence motif content of enhancers, and to drive targeted reporter or effector protein expression in experimental applications. Furthermore, we used epigenomic analysis of human and mouse cortex tissue to directly compare the genome‐wide enhancer architecture in these species. This atlas provides a primary resource for investigating gene regulatory mechanisms of telencephalon development and enables studies of the role of distant‐acting enhancers in neurodevelopmental disorders.

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Granulins Regulate Aging Kinetics in the Adult Zebrafish Telencephalon

Project description:Granulins (GRN) are secreted factors that promote neuronal survival and regulate inflammation in various pathological conditions. However, their roles in physiological conditions in the brain remain poorly understood. To address this knowledge gap, we analysed the telencephalon in Grn-deficient zebrafish and identified morphological and transcriptional changes in microglial cells, indicative of a pro-inflammatory phenotype in the absence of any insult. Unexpectedly, activated mutant microglia shared part of their transcriptional signature with aged human microglia. Furthermore, transcriptome profiles of the entire telencephali isolated from young Grn-deficient animals showed remarkable similarities with the profiles of the telencephali isolated from aged wildtype animals. Additionally, 50% of differentially regulated genes during aging were regulated in the telencephalon of young Grn-deficient animals compared to their wildtype littermates. Importantly, the telencephalon transcriptome in young Grn-deficent animals changed only mildly with aging, further suggesting premature aging of Grn-deficient brain. Indeed, Grn loss led to decreased neurogenesis and oligodendrogenesis, and to shortening of telomeres at young ages, to an extent comparable to that observed during aging. Altogether, our data demonstrate a role of Grn in regulating aging kinetics in the zebrafish telencephalon, thus providing a valuable tool for the development of new therapeutic approaches to treat age-associated pathologies.

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