Murine Müllrian duct Day0 DES
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE1886 | GEO | 2004/10/28
SECONDARY ACCESSION(S): PRJNA90525
REPOSITORIES: GEO
Similar Datasets
Project description:Diethylstilbestrol (DES) inhibits the differentiation of female reproductive tracts during fetal and neonatal days . We examined global gene expressions in the oviduct, uterus and vagina in newborn mice with or without DES. These results suggest understanding the mechanism of the differentiation of female reproductive tracts. Keywords: ordered
2004-10-28 | E-GEOD-1886 | biostudies-arrayexpress
Project description:DES is a synthetic estrogen that is associated with adverse effects on reproductive organs. Our group has employed estrogen receptor (ER) α knockout (αERKO) mice to gain insight into the contribution of ER-dependent pathways in mediating the effects of neonatal DES exposure in female and male reproductive tract tissues. The objective of this study is to compare gene expression profiles between the WT-veh and -DES groups or αERKO-veh and -DES from the adult male mice (week 10) of the SV tissues to identify differential genes.
2018-03-27 | GSE95314 | 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.
2012-05-15 | GSE37969 | GEO
Project description:The main objective of the FREIA project is to identify markers of endocrine disrupting effects in rodents to overcome the lack of sensitive markers of female reproductive toxicity. For that 2 archetypes of endocrine disruption are studied, ketoconazole (KTZ) and diethylstilbestrol (DES) at three different stages (post-natal days 6, 14, and 22) and at three different doses 3, 6 and 12 milligram per kilogram by bodyweight per day for KTZ and 3, 6 and 12 microgram per kilogram for DES.
2023-03-08 | GSE208545 | GEO
Project description:The aim of the study was to assess the cellular composition and transcriptional changes at single-cell resolution of the female reproductive tract across the four stages of estrus cycle in young adult mice (ovary, oviduct, uterus, cervix and vagina, with spleen as a comparison) and compared this with similar analyses of decidualization (uterus) and ageing (ovary, oviduct, uterus, cervix, vagina and spleen). Vaginal smears were used to stage the estrus cycle in young mice. To collect the decidualized uteri mice were mated and uterine tissue was collected from pregnant mice at day 5.5 after mating. Tissues of aged mice were collected at the age of 18 months. All tissues were collected and digested using a collagenase and trypsin protocol to obtain single cell suspension. Libraries were prepared using the 10x scRNA-seq protocol.
2023-02-01 | E-MTAB-11491 | biostudies-arrayexpress
Project description:Three independent replicates of 4 groups of immature (19/20 days of age) Alpk:APfCD-1 mice were treated with arachis oil (AO) vehicle, 2.5ug/kg 17beta-estradiol (E2), 2ug/kg diethylstilbestrol (DES), or 50mg/kg genistein (GEN), via 3 daily subcutaneous injection, and sacrificed 72hr after initial dose. Keywords: other
2004-10-14 | GSE1839 | GEO
Project description:Previously, we described a mouse model where the well-known reproductive carcinogen, diethylstilbestrol (DES), caused uterine adenocarcinoma following neonatal treatment. Tumor incidence was dose-dependent reaching >90% by 18 mo. following 1000 µg/kg/day of DES. These tumors followed the initiation/promotion model of hormonal carcinogenesis with developmental exposure as the initiator, and exposure to ovarian hormones at puberty as the promoter. To identify molecular pathways involved in DES-initiation events, uterine gene expression profiles were examined in prepubertal mice exposed to DES (1, 10 or 1000 µg/kg/day) on days 1-5 and compared to age-matched controls. Of more than 20,000 transcripts, approximately 3% were differentially expressed in at least one DES treatment group compared to controls; several transcripts demonstrated dose-responsiveness. Assessment of gene ontology annotation revealed alterations in genes associated with cell growth, differentiation, and adhesion. When expression profiles were compared to published studies of uteri from 5 day old DES-treated mice, or adult mice treated with 17β estradiol, similarities were seen suggesting persistent differential expression of estrogen responsive genes following developmental DES exposure. Moreover, several significantly altered genes have been identified in human uterine adenocarcinomas. Four altered genes [Lactotransferrin (Ltf), Transforming growth factor beta inducible (Tgfβ1), Cyclin D1 (Ccnd1), and Secreted frizzled-related protein 4 (Sfrp4)], selected for real time RT-PCR analysis, correlated well with the directionality of the microarray data. These data suggest altered gene expression profiles observed two weeks after treatment ceased, were imprinted at the time of developmental exposure and maybe related to the initiation events resulting in carcinogenesis. Keywords: dose reponse
2007-06-14 | GSE5825 | GEO
Project description:Neonatal exposure to diethylstilbestrol (DES) results in abnormal reproductive tract morphology, female infertility and uterine cancer in mice. This exposure also causes altered gene expression in the female reproductive tract that persists into adulthood. To further explore on a genome-wide basis how neonatal estrogen exposure results in permanent epigenetic changes, we performed RNA-seq and ChIP-seq analyses of DES-treated and control mice. CD-1 mice were treated on postnatal days (PND) 1-5 with DES (2 µg/pup/day) or corn oil as a control; uterine tissues were collected on PND5. RNA-seq analysis resulted in 4,498 differentially expressed genes (>1.5 fold difference; RPKM >1; FDR <0.05). ChIP-seq was performed on uterine samples using H3K4me3, H3K27me3, H3K27acetyl and H3K4me1 as the precipitating antibodies. The most significant findings at the TSS were increased H3K4me3 at up-regulated genes (22%), increased H3K27ac at up-regulated genes (55%) and differential H3K27ac at down-regulated genes (33%). The most striking finding was differential association of H3K27ac at presumed enhancer regions; 3,012 out of 4498 altered genes (67%) had a differential H3K27ac peak associated with them and 2,962 out of 4,498 (66%) had differential H3K4me1. These differences were generally coordinated with gene expression with increased gene expression having more H3K27ac associated although a small subset of genes showed the opposite. To further investigate the mechanism of differential H3K27ac binding in enhancer regions near estrogen regulated genes, we overlapped these enhancers to Esr1 ChIP seq data; a large percentage of them overlap with Esr1 peaks (39%). We also performed motif analysis where ERE was enriched in the differential H3K27ac peaks. We further investigated Esr1’s role in differential H3K27ac enhancer binding by using a conditional uterine deletion of Esr1 by crossing Esr1 floxed mice with PgR-cre and then treating with vehicle or DES and collecting uteri on day 5. We performed a microarray and pattern analysis and determined there were 4,073 out of 4,617 altered genes (88%) protected by conditional uterine deletion of Esr1. We also performed H3K27ac ChIP seq on these samples and found a large number of these protected genes have a differential H3K27ac enhancer. Several Fox genes were up-regulated following DES treatment and Fox binding motifs were found to be enriched in both H3K27ac and H3K4me1 differential enhancer peaks. To further study the impact of Foxa2 or Foxo1, we conditionally deleted each of these using PgR-cre. There were far fewer genes impacted by deletion of either Foxa2 or Foxo1 suggesting these Fox genes are not responsible for DES induced gene expression and these two lines were not followed further. Taken together, these data suggest estrogen regulates gene expression in the neonatal mouse uterus by H3K27ac association at Esr1 binding sites near estrogen regulated genes. Changes in the epigenome during the time of treatment may contribute to the permanent alterations in gene expression observed in aged DES treated mice.
2018-03-27 | GSE97073 | 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:Because perinatal exposure to diethylstilbestrol (DES; strong estrogen) or ketoconazole (KTZ; steroidogenesis inhibitor) delayed vaginal opening and GnRH secretion in female rats, we studied the hypothalamic transcriptome to identify their target genes.
2023-03-21 | GSE225359 | GEO