Inhibin knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells.
Defective gonadotropin-dependent ovarian folliculogenesis and granulosa cell gene expression in inhibin-deficient mice.
Specimen part, Treatment
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Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment.
Sex
View SamplesIn this study, we tested if miRNAs are altered in amygdala and ventral striatum as a consequence of prenatal ethanol exposure and/or social enrichment. miRNA samples from 72 male and female adolescent rats were analyzed by RNA-Seq analysis and Affymetrix miRNA arrays. Several miRNAs showed significant changes due to prenatal ethanol exposure or social enrichment in one or both brain regions. Some of the miRNA changes caused by ethanol were reversed by social enrichment. The top predicted gene targets of these miRNAs were mapped and subjected to pathway enrichment analysis. We also directly examined the evidence for modulation of target mRNAs in whole transcriptome microarray data from the same rats. Among the pathways most strongly affected were p53, CREB, Glutamate and GABA signaling. Together, our data suggest a number of novel epigenetic mechanisms for social enrichment to reverse the effects of ethanol exposure.
Effects of Acute Prenatal Exposure to Ethanol on microRNA Expression are Ameliorated by Social Enrichment.
Sex
View SamplesTo compare the RNAs present in dendrites and somas of individual neurons, we manually separated the dendrites and soma of primary mouse hippocampal neurons using a micropipette and performed RNA-sequencing on each subcellular fraction such that we obtained the subcellular transcriptomes of the same cell. Overall design: 16 individual neurons were collected and dissected (yielding a total of 32 soma and dendrite samples) from multiple cultures across multiple days. ERCC spike-in control RNA was added to each sample.
Comprehensive catalog of dendritically localized mRNA isoforms from sub-cellular sequencing of single mouse neurons.
Cell line, Subject
View SamplesEthanol inhibits the proliferation of neural stem cells in the fetal, adolescent, and adult brain. The consequences are cognitive deficits associated with fetal alcohol spectrum disorder and alcohol use disorder. We tested the hypothesis that ethanol affects progression through cell cycle checkpoints by differentially modifying transcriptional processes. Monolayer cultures of NS-5 neural stem cells were treated for 48 hr with the mitogenic agent FGF2 or the anti-mitogenic TGF1 in the absence or presence of ethanol. Cell cycle elongation was induced by a global down-regulation of genes involved in cell cycle progression, including the cyclin E system. Checkpoint regulation occurred downstream of p21 and Jun-oncogene signaling cascades. Thus, ethanol can affect cell cycle progression by altering transcript expression of strategic genes downstream of the G1/S checkpoint.
Ethanol-induced methylation of cell cycle genes in neural stem cells.
Specimen part, Treatment
View SamplesTranscriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View SamplesPost mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View SamplesPost mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View SamplesPost mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sex, Age, Disease, Disease stage
View SamplesPurpose: Investigate the molecular determinants of retinal regeneration in adult vertebrates by analyzing the gene expression profiles of control and post-lesion retina of adult zebrafish, a system that regenerates following injury.
Gene expression profiles of intact and regenerating zebrafish retina.
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