The role of estrogen and testosterone in the regulation of gene expression in the proximal reproductive tract is not completely understood. To address this question, mice were treated with testosterone or estradiol and RNA from the efferent ducts and caput epididymis was processed and hybridized to Affymetrix MOE 430 2.0 microarrays. Analysis of array output identified probe sets in each tissue with altered levels in hormone treated versus control animals. Hormone treatment efficacy was confirmed by determination of serum hormone levels pre- and post-treatment and observed changes in transcript levels of previously reported hormone-responsive genes. Tissue-specific hormone sensitivity was observed with 2867 and 3197 probe sets changing significantly in the efferent ducts after estrogen and testosterone treatment, respectively. In the caput epididymis, 117 and 268 probe sets changed after estrogen and testosterone treatment, respectively, demonstrating a greater response to hormone in the efferent ducts than the caput epididymis. Transcripts sharing similar profiles in the intact and hormone-treated animals compared with castrated controls were also identified. Ontological analysis of probe sets revealed a significant number of hormone-regulated transcripts encode proteins associated with lipid metabolism, transcription and steroid metabolism in both tissues. Real-time RT-PCR was employed to confirm array data and investigate other potential hormone-responsive regulators of proximal reproductive tract function. The results of this work reveal previously unknown responses to estrogen in the caput epididymis and to testosterone in the efferent ducts as well as tissue specific hormone sensitivity in the proximal reproductive tract.
Regulation of gene expression by estrogen and testosterone in the proximal mouse reproductive tract.
Sex, Specimen part, Treatment
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Profiling gene expression during the differentiation and development of the murine embryonic gonad.
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View SamplesTime course of gene expression in the murine embryonic ovary from the time of the indifferent gonad (11.5dpc) to birth (18.5dpc)
Profiling gene expression during the differentiation and development of the murine embryonic gonad.
No sample metadata fields
View SamplesTime course of gene expression in the murine embryonic testis from the time of the indifferent gonad (11.5dpc) to birth (18.5dpc)
Profiling gene expression during the differentiation and development of the murine embryonic gonad.
No sample metadata fields
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Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesTranscriptional profiles of Fz4-/- retinal endothelial cells were compared to that of wild type endothelial cells under various culture conditions. The goal was to identify the transcriptional response to Frizzled 4 signaling in cultured retinal endothelial cells. To analyze the Norrin response of WT and Fz4-/- retinal endothelial cells in culture, we co-cultured these cells either with HEK293 cell line that stably expresses Norrin or with control 293 cells.
Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesTo characterize the long-term effect on the transcriptome of a decrement in Norrin/Fz4/Lrp signaling, microarray hybridization was performed with RNA from acutely dissociated and anti-PECAM immunoaffinity-purified adult WT, Fz4-/-, Lrp5-/-, and Norrin- retinal vascular cells.
Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesTranscriptional profiles of the embryonic yolk sac from embryos with ectopic Norrin expression were compared to their wild type littermate controls. The goal is to identify the transcriptional response to Norrin-Frizzled 4 signaling during embryonic angiogenesis.
Norrin, frizzled-4, and Lrp5 signaling in endothelial cells controls a genetic program for retinal vascularization.
Sex, Specimen part
View SamplesPhosphorylation and subsequent nuclear translocation of SMAD proteins determine the cellular response to activin. Here we identify a novel means by which activin signalling is regulated to enable developmental stage-specific SMAD gene transcription. In response to activin A, immature proliferating mouse Sertoli cells exhibit nuclear accumulation of SMAD3, but not SMAD2, although both proteins are phosphorylated. In post-mitotic differentiating cells, both SMAD2 and SMAD3 accumulate in the nucleus. Furthermore, immature Sertoli cells are sensitive to activin dosage; at higher concentrations maximal SMAD3 nuclear accumulation is observed, accompanied by a small, but significant, increase in nuclear SMAD2. Microarray analysis confirmed that differential SMAD utilization correlated with altered transcriptional outcomes and identified new activin target genes, Gja1 and Serpina5, which are known to be required for Sertoli cell development and male fertility. In immature Sertoli cells, genetic or transient knockdown of SMAD3 enhanced SMAD2 nuclear accumulation in response to activin, with increased Serpina5 mRNA levels associated with nuclear localized SMAD2. In transgenic mice with altered activin bioactivity that display male fertility phenotypes, testicular Gja1 and Serpina5 mRNA levels reflected altered in vivo activin levels. We conclude that regulated nuclear accumulation of phosphorylated SMAD2 is a novel determinant of developmentally regulated activin signalling.
Developmentally regulated SMAD2 and SMAD3 utilization directs activin signaling outcomes.
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Genome-wide identification of Ikaros targets elucidates its contribution to mouse B-cell lineage specification and pre-B-cell differentiation.
Specimen part, Cell line
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