Genomic, proteomic, and metabolomic technologies continue to receive increasing interest from environmental toxicologists. This interest is due to the great potential of these technologies to identify detailed modes of action and to provide assistance in the evaluation of a contaminant’s risk to aquatic organisms. Our experimental model is the zebrafish (Danio rerio) exposed to reference endocrine disrupting compounds in order to investigate compound-induced changes in gene transcript profiles. Adult, female zebrafish were exposed to 0, 15, 40, and 100 ng/L of 17 alpha-ethynylestradiol (EE2) and concentration and time-dependent changes in hepatic gene expression were examined using Affymetrix GeneChip® Zebrafish Genome Microarrays. At 24, 48, and 168 hours, fish were sacrificed and liver mRNA was extracted for gene expression analysis (24 and 168 hours only). In an effort to link gene expression changes to effects on higher levels of biological organization, body and ovary weights were measured and blood was collected for measurement of plasma steroid hormones (17 beta-estradiol (E2), testosterone (T)) and vitellogenin (VTG) using ELISA. EE2 exposure significantly affected GSI, E2, T, VTG and gene expression. We observed 1575 genes that were significantly affected (up- or down-regulated by at least 1.5-fold (p ? 0.001) in a concentration-dependent manner by EE2 exposure at either 24 or 168 hours. EE2 exposure altered transcription of genes involved in steroid hormone homeostasis, cholesterol homeostasis, retinoic acid metabolism, and cell growth and proliferation. Plasma VTG was significantly increased at 24, 48, and 168 hours (p<0.05) at 40 and 100 ng/L and at 15 ng/L at 168 hours. E2 and T were significantly reduced following EE2 exposure at 48 and 168 hours. GSI was decreased in a dose-dependent manner at 168 hours. In this study, we identified genes involved in a variety of biological functions that have the potential to be used as markers of exposure to estrogenic substances. Future work will evaluate the use of these genes in zebrafish exposed to weak estrogens to determine if these genes are indicative of exposure to estrogens with varying potencies.
Hepatic gene expression profiling using Genechips in zebrafish exposed to 17alpha-ethynylestradiol.
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Sex, Specimen part, Compound, Time
View SamplesProteinases play a pivotal role in wound healing by degrading molecular barriers, regulating cell-matrix interactions and availability of bioactive molecules. Matrix metalloproteinase-13 (MMP-13, collagenase-3) is a wide spectrum proteinase. Its expression and function is linked to the growth and invasion of many epithelial cancers such as squamous cell carcinoma. Moreover, the physiologic expression of MMP-13 is associated e.g. to scarless healing of human fetal skin and adult gingival wounds. While MMP-13 is not found in the normally healing skin wounds in human adults, it is expressed in mouse skin during wound healing. Thus, mouse wound healing models can be utilized for studying the role of MMP-13 in the events of wound healing. As the processes such as the migration and proliferation of keratinocytes, angiogenesis, inflammation and activation of fibroblasts are components of wound repair as well as of cancer, many results received from wound healing studies are also adaptable to cancer research.
MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.
Time
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View SamplesThe SAGA co-activator has been implicated in the regulation of a smal subset of genes in budding yeast in transcriptomic analyses performed in steady-state levels of RNA.
SAGA Is a General Cofactor for RNA Polymerase II Transcription.
Genetic information
View Samples