High dose level dibutyl phthalate (DBP) exposure of fetal rat testes in vivo inhibits testosterone production (i.e. endocrine disruption). Here, fetal testis mRNA levels were profiled following exposure to a DBP dose level that did not significantly reduce testosterone levels. The goal was to identify the constellation of gene expression changes that do not correlate with endocrine disruption.
Species-specific dibutyl phthalate fetal testis endocrine disruption correlates with inhibition of SREBP2-dependent gene expression pathways.
Sex, Specimen part
View SamplesInterstitial cystitis (IC), a chronic bladder disease with an increasing incidence, is diagnosed using subjective symptoms in combination with cystoscopic and histological evidence. The ultimate goal is the development of a diagnostic assay for IC on a molecular level.
Gene expression profile of bladder tissue of patients with ulcerative interstitial cystitis.
Specimen part, Disease, Disease stage
View SamplesIn contrast to the well-established role of oxidative muscle fibers in regulating fatty acid oxidation and whole body metabolism, little is known that about the function of fast/glycolytic muscle fibers in these processes. Here, we generated a skeletal muscle-specific, conditional transgenic mouse expressing a constitutively-active form of Akt1. Transgene activation led to muscle hypertrophy due to the growth of type IIb muscle fibers, which was accompanied by an increase in strength. These mice were then used to assess the consequence of building fast/glycolytic muscle fibers on adiposity and metabolism. Akt1 transgene induction in obese mice resulted in reductions in body weight and fat mass, a resolution of hepatic steatosis and improved metabolic parameters. These effects were achieved independent of changes in physical activity and levels of food consumption. Akt1-mediated skeletal muscle growth opposed the effects of high fat/sucrose diet on transcript expression patterns in the liver, and increased hepatic fatty acid oxidation and ketone body production. Our findings indicate that an increase in fast/glycolytic muscle mass can result in the regression of obesity and obesity-related metabolic disorders in part through its ability to alter fatty acid metabolism in remote tissues.
Fast/Glycolytic muscle fiber growth reduces fat mass and improves metabolic parameters in obese mice.
Sex, Specimen part, Treatment
View SamplesWe analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus, neocortex, and cerebellum to determine estrous cycle-specific changes in these four brain regions. We found almost 16,000 genes are present in one or more of the brain areas but only 210 genes, ~1.3%, are significantly changed as a result of the estrous cycle. The hippocampus has the largest number of differentially expressed genes (DEGs) (82), followed by the neocortex (76), hypothalamus (63), and cerebellum (26). Most of these DEGs (186/210) are differentially expressed in only one of the four brain regions. A key finding is the unique expression pattern of growth hormone (Gh) and prolactin (Prl). Gh and Prl are the only DEGs to be expressed during only one stage of the estrous cycle (metestrus). To gain insight into the function of the DEGs, we examined gene ontology and phenotype enrichment and found significant enrichment for genes associated with myelination, hormone stimulus, and abnormal hormone levels. Additionally, 61 of the 210 DEGs are known to change in response to estrogen in the brain. 50 genes differentially expressed as a result of the estrous cycle are related to myelin and oligodendrocytes and 12 of the 63 DEGs in the hypothalamus are oligodendrocyte- and myelin-specific genes. This transcriptomic analysis reveals that gene expression in the female mouse brain is remarkably stable during the estrous cycle and demonstrates that the genes that do fluctuate are functionally related. Overall design: Hypothalamus, hippocampus, neocortex, and cerebellum mRNA from adult female C57BL/6J (B6) mice were analyzed by RNA sequencing of 3 biological replicates for each of the 4 stages of the estrous cycle using an Illumina HiSeq 2500
The stability of the transcriptome during the estrous cycle in four regions of the mouse brain.
Sex, Age, Specimen part, Cell line, Subject
View SamplesA variety of neurological disorders, including Alzheimer's disease, Parkinson's disease, major depressive disorder, dyslexia and autism, are differentially prevalent between females and males. To better understand the possible molecular basis for the sex-biased nature of neurological disorders, we measured both mRNA and protein in the hippocampus of female and male mice at 1, 2, and 4 months of age with RNA-sequencing and mass-spectrometry respectively. Differential expression analyses identify 2699 genes that are differentially expressed between animals of different ages. 198 transcripts are differentially expressed between females and males at one or more ages. The number of transcripts that are differentially expressed between females and males is greater in adult animals than in younger animals. Additionally, we identify 69 transcripts that show complex and sex-specific patterns of temporal regulation across all ages, 8 of which are heat-shock proteins. We also find a modest correlation between levels of mRNA and protein in the mouse hippocampus (Rho = 0.53). This study adds to the substantial body of evidence for transcriptomic regulation in the hippocampus during postnatal development. Additionally, this analysis reveals sex differences in the transcriptome of the developing mouse hippocampus, and further clarifies the need to include both female and male mice in longitudinal studies involving molecular changes in the hippocampus. Overall design: Hippocampal mRNA from 1, 2, and 4 month old male and female B6 mice were analyzed by RNA sequencing of 5 biological replicates using an Illumina HiSeq 2500
Sex differences in the molecular signature of the developing mouse hippocampus.
Sex, Age, Specimen part, Cell line, Subject
View SamplesThe objective was to study the transcriptomic changes in adipose tissue in the early stages of lactation, specifically in Bos Taurus, Holstein dairy cattle as a function of milk production and genetic merit.
Differential expression of genes in adipose tissue of first-lactation dairy cattle.
Specimen part
View SamplesNumerous neurological disorders, including Alzheimer's disease, display a sex-biased prevalence. To identify molecular correlates of this sex bias, we investigated sex-differences in molecular pathology in the hippocampus using the 5XFAD mouse model of Alzheimer's disease during early stages of disease progression (1, 2, and 4 months of age). Overall design: Hippocampal mRNA from 1, 2, and 4 month old male and female 5XFAD mice were analyzed by RNA sequencing of 5 biological replicates using an Illumina HiSeq 2500
Sex-biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease: A multi-omic analysis.
Sex, Age, Specimen part, Cell line, Subject
View SamplesWhile identification of genes mutated in high penetrance tumor predisposition syndromes has been a success story, much less progress has been made in characterizing the genetic basis of low penetrance tumor susceptibility. Combining recently introduced chip-based technologies with traditional genealogy work we have identified inactivating germline mutations in patients with pituitary adenoma predisposition (PAP).
Pituitary adenoma predisposition caused by germline mutations in the AIP gene.
No sample metadata fields
View SamplesIdentifying sex differences in gene expression within the brain is critical for determining why multiple neurological and behavioral disorders differentially affect males and females. Several are more common or severe in males (e.g., autism and schizophrenia) or females (e.g., Alzheimer’s disease and depression). We analyzed transcriptomic data from the mouse hippocampus of six inbred strains (129S1/SvImJ, A/J, C57BL/6J, DBA/1J, DBA/2J and PWD/Ph), to provide a perspective on differences between male and female gene expression. Our data show that: 1) significant gene expression differences in males versus females varies substantially across the strains, 2) 12 genes exist that are differentially expressed across the inbred strains (termed core genes), and 3) there are >2,600 significantly differentially expressed genes (DEGs) among the strains (termed non-core genes). We found that DBA/2J uniquely has a substantial majority (89%) of DEGs that are more highly expressed in females than males; 129/SvImJ is the most strongly male-biased with a majority (69%) of DEGs that are more highly expressed in males. To gain insight into the sex-biased DEGs, we examined gene ontology, pathway and phenotype enrichment and found significant enrichment in phenotypes related to abnormal nervous system morphology and physiology, among others. In addition, several pathways are enriched significantly, including Alzheimer’s disease (AD), with 32 genes implicated in AD, 8 of which are male-biased. Three of the male-biased genes have been implicated in a neuroprotective role in AD. Our transcriptomic data provide new insight into understanding the possible genetic bases for sex-specific susceptibility and severity of brain disorders. Overall design: Hippocampal mRNA from adult males and females of six inbred strains of mice were analyzed by RNA sequencing of 3 biological replicates using an Illumina HiSeq 2500
Transcriptomic analysis of the hippocampus from six inbred strains of mice suggests a basis for sex-specific susceptibility and severity of neurological disorders.
Sex, Age, Specimen part, Cell line, Subject
View SamplesComparative genome wide gene expression profiles of small and large luteal cells from characterized mature CL are not currently available in any species. During present study, transcriptome differences of small and large luteal cells werte comprehensively analyzed to understand the specific functional roles of small and large luteal cells in mature bovine CL.
<i>mRNA</i> microarray data of FACS purified bovine small and large luteal cells.
Specimen part
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