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
View SamplesWe have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Overall design: Examination of blood component in 20 different time points over 1.5 years which includes 2 disease state and 18 healty state Related exome studies at: SRX083314 SRX083313 SRX083312 SRX083311
Personal omics profiling reveals dynamic molecular and medical phenotypes.
Specimen part, Disease, Subject
View SamplesGinkgo biloba leaf extract (GBE) has been used for centuries in traditional Chinese medicine and today is used as an herbal supplement for various indications such as improving neural function, anti-oxidant and anti-cancer effects. As part of the herbal supplement industry, these compounds are largely unregulated, and may be consumed in large concentrations over extended periods of time. This is of particular concern, because the long-term effects in terms of toxicity and carcinogenicity data is lacking for many herbal products, including GBE. The 2-year B6C3F1 mouse carcinogenicity bioassay indicated a marked dose-related increase in hepatocellular carcinoma (HCC) development associated with exposure to GBE. We have shown that the mechanism of this increase in tumorigenesis is related to a marked increase in the incidence of -catenin mutation, and report a novel mechanism of constitutive -catenin activation through post-translational modification leading to constitutive Wnt signaling and unregulated growth signaling and oncogenesis. Furthermore, using global gene expression profiling, we show that GBE-induced HCC exhibit overrepresentation of gene categories associated with human cancer and HCC signaling including upregulation of relevant oncogenes and suppression of critical tumor suppressor genes, as well as chronic oxidative stress, a known inducer of calpain-mediated degradation and promoter of hepatocarcinogenesis in humans. These data provide a molecular mechanism to GBE-induced HCC in B6C3F1 mice that is relevant to human cancer, and provides relevant molecular data that will provide the groundwork for further risk assessment of unregulated compounds, including herbal supplements.
Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways.
Specimen part
View SamplesAnalyzing the kenetics of alveolar macrophage turnover after human lung transplantation and identifying protein and transcriptional differences between donor and recipient-derived alveolar macrophages Overall design: Bulk RNA sequencing performed from FACS sorted donor and recipient-derived alveolar macrophages derived from the bronchoalveolar lavage of lung transplant recipients, defined as CD45+, Live, lineage negative, CD64+CD206+ cells.
Rate of recipient-derived alveolar macrophage development and major histocompatibility complex cross-decoration after lung transplantation in humans.
Specimen part, Subject
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