Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA166857 | ENA |
REPOSITORIES: ENA
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Project description:Developmental exposure to diethylstilbestrol (DES) causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of the Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma)-mediated adipogenic/lipid metabolic pathway, including PPARgamma itself, are targets of DES in the neonatal uterus. TEM and Oil Red O staining further demonstrate a dramatic increase in lipid deposition in the uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor induced reproductive abnormalities.
2012-05-15 | GSE37969 | GEO
Project description:Developmental exposure to diethylstilbestrol (DES) causes reproductive tract malformations, affects fertility and increases the risk of clear cell carcinoma of the vagina and cervix in humans. Previous studies on a well-established mouse DES model demonstrated that it recapitulates many features of the human syndrome, yet the underlying molecular mechanism is far from clear. Using the neonatal DES mouse model, the present study uses global transcript profiling to systematically explore early gene expression changes in individual epithelial and mesenchymal compartments of the neonatal uterus. Over 900 genes show differential expression upon DES treatment in either one or both tissue layers. Interestingly, multiple components of the Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma)-mediated adipogenic/lipid metabolic pathway, including PPARgamma itself, are targets of DES in the neonatal uterus. TEM and Oil Red O staining further demonstrate a dramatic increase in lipid deposition in the uterine epithelial cells upon DES exposure. Neonatal DES exposure also perturbs glucose homeostasis in the uterine epithelium. Some of these neonatal DES-induced metabolic changes appear to last into adulthood, suggesting a permanent effect of DES on energy metabolism in uterine epithelial cells. This study extends the list of biological processes that can be regulated by estrogen or DES, and provides a novel perspective for endocrine disruptor induced reproductive abnormalities. We separated UE from the UM from vehicle (oil)- or DES-treated postnatal day 5 (P5) mice, and prepared biological triplicates of RNA from pooled specimens (nM-bM-^IM-%3). Those samples were analyzed on two MouseWG-6 BeadChips, which detects 45,200 transcripts including more than 26,000 annotated genes in the NCBI RefSeq database. Difference of at least twofold in signal intensity of each given probe set with a P-value less than 0.05 was considered statistically significant.
2012-05-14 | E-GEOD-37969 | biostudies-arrayexpress
Project description:Developmental exposure to non-mutagenic environmental factors can contribute to cancer risk, but the underlying mechanisms are not understood. We used a mouse model of endometrial adenocarcinoma that results from brief developmental exposure to an estrogenic chemical, diethylstilbestrol (DES), to determine causative factors. Single cell RNA sequencing and spatial transcriptomics of adult uteri revealed new markers of uterine epithelial stem cells, identified luminal and glandular progenitor cells, and defined a glandular epithelial differentiation trajectory. Neonatal DES exposure disrupted uterine epithelial differentiation, resulting in widespread activation of Wnt signaling and a failure to generate epithelial stem cells or distinguishable glandular and luminal epithelial cells. The endometrial stromal cells activated inflammatory signals and oxidative stress. Together, these changes activated PI3K/AKT signaling to drive malignant transformation. These findings explain how human cancers, which are often associated with abnormal activation of PI3K/AKT signaling, could result from exposure to environmental insults during development.
2023-08-11 | GSE218156 | GEO
Project description:PURPOSE: To provide a detailed gene expression profile of the normal postnatal mouse cornea. METHODS: Serial analysis of gene expression (SAGE) was performed on postnatal day (PN)9 and adult mouse (6 week) total corneas. The expression of selected genes was analyzed by in situ hybridization. RESULTS: A total of 64,272 PN9 and 62,206 adult tags were sequenced. Mouse corneal transcriptomes are composed of at least 19,544 and 18,509 unique mRNAs, respectively. One third of the unique tags were expressed at both stages, whereas a third was identified exclusively in PN9 or adult corneas. Three hundred thirty-four PN9 and 339 adult tags were enriched more than fivefold over other published nonocular libraries. Abundant transcripts were associated with metabolic functions, redox activities, and barrier integrity. Three members of the Ly-6/uPAR family whose functions are unknown in the cornea constitute more than 1% of the total mRNA. Aquaporin 5, epithelial membrane protein and glutathione-S-transferase (GST) omega-1, and GST alpha-4 mRNAs were preferentially expressed in distinct corneal epithelial layers, providing new markers for stratification. More than 200 tags were differentially expressed, of which 25 mediate transcription. CONCLUSIONS: In addition to providing a detailed profile of expressed genes in the PN9 and mature mouse cornea, the present SAGE data demonstrate dynamic changes in gene expression after eye opening and provide new probes for exploring corneal epithelial cell stratification, development, and function and for exploring the intricate relationship between programmed and environmentally induced gene expression in the cornea. Keywords: other
2004-01-02 | GSE887 | GEO
Project description:Abstract. Very little is known regarding how hormonal exposures impact the epigenetic landscape of developing tissues in the context of a whole organism, in contrast to the impact on cultured cells. Here we took a global approach to understanding how neonatal exposure to the xenoestrogen, diethylstilbestrol (DES), alters the uterine epigenome. RNA-seq and ChIP-seq (H3K4me3, H3K27me3, H3K27ac and H3K4me1) were performed on DES-treated and control uteri. The most striking finding was differential association of H3K27ac and H3K4me1 at typical and super-enhancer regions of 79% of altered genes. These peaks overlapped with previously reported estrogen receptor a (ERα) ChIP-seq peaks. Conditional uterine deletion of ERα (Esr1cKO) conferred protection of 88% of altered genes. H3K27ac ChIP-seq on Esr1cKO samples showed that 72% of protected genes had a differential H3K27ac enhancer. These data suggest that DES regulates gene expression in the neonatal mouse uterus by H3K27ac association at ERα binding sites near estrogen-regulated genes.
2018-03-27 | GSE104401 | GEO
Project description:Abstract. Very little is known regarding how hormonal exposures impact the epigenetic landscape of developing tissues in the context of a whole organism, in contrast to the impact on cultured cells. Here we took a global approach to understanding how neonatal exposure to the xenoestrogen, diethylstilbestrol (DES), alters the uterine epigenome. RNA-seq and ChIP-seq (H3K4me3, H3K27me3, H3K27ac and H3K4me1) were performed on DES-treated and control uteri. The most striking finding was differential association of H3K27ac and H3K4me1 at typical and super-enhancer regions of 79% of altered genes. These peaks overlapped with previously reported estrogen receptor a (ERα) ChIP-seq peaks. Conditional uterine deletion of ERα (Esr1cKO) conferred protection of 88% of altered genes. H3K27ac ChIP-seq on Esr1cKO samples showed that 72% of protected genes had a differential H3K27ac enhancer. These data suggest that DES regulates gene expression in the neonatal mouse uterus by H3K27ac association at ERα binding sites near estrogen-regulated genes.
2018-03-27 | GSE104400 | GEO
Project description:Uterine Transcriptional Profile Following Treatment with Estradiol or Synthetic Estrogens Diethylstilbestrol and Propyl Pyrazole Triol
| PRJNA262681 | ENA
Project description:To describe the protein profile in hippocampus, colon and ileum tissue’ changing after the old faeces transplants, we adopted a quantitative label free proteomics approach.
2021-09-09 | PXD016432 | Pride
Project description:Introgressed variants from other species can be an important source of genetic variation because they may arise rapidly, can include multiple mutations on a single haplotype, and have often been pretested by selection in the species of origin. Although introgressed alleles are generally deleterious, several studies have reported introgression as the source of adaptive alleles-including the rodenticide-resistant variant of Vkorc1 that introgressed from Mus spretus into European populations of Mus musculus domesticus. Here, we conducted bidirectional genome scans to characterize introgressed regions into one wild population of M. spretus from Spain and three wild populations of M. m. domesticus from France, Germany, and Iran. Despite the fact that these species show considerable intrinsic postzygotic reproductive isolation, introgression was observed in all individuals, including in the M. musculus reference genome (GRCm38). Mus spretus individuals had a greater proportion of introgression compared with M. m. domesticus, and within M. m. domesticus, the proportion of introgression decreased with geographic distance from the area of sympatry. Introgression was observed on all autosomes for both species, but not on the X-chromosome in M. m. domesticus, consistent with known X-linked hybrid sterility and inviability genes that have been mapped to the M. spretus X-chromosome. Tract lengths were generally short with a few outliers of up to 2.7 Mb. Interestingly, the longest introgressed tracts were in olfactory receptor regions, and introgressed tracts were significantly enriched for olfactory receptor genes in both species, suggesting that introgression may be a source of functional novelty even between species with high barriers to gene flow.
| S-EPMC8784167 | biostudies-literature
Project description:Neonatal morphine exposure alters mRNA and microRNA (miR) expression in mouse hippocampus
| PRJNA263916 | ENA