Transcription profiling of rat uterine myometrium -effect of estrogen
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Dora Agbas
PROVIDER: E-GEOD-9117 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Uterine tissue is highly responsive to estrogen, which plays a mayor role in sympathetic innervation remodeling in myometrium Microarrays were used to investigate which estrogen resposive myometrial proteins can be involved in innervation modulation Keywords: control vs. treatment, timepoints
2007-09-21 | GSE9117 | GEO
Project description:Context: Increased uterine stretch appears to increase the risk of preterm labour, but the mechanism is unknown. Objectives: To identify a targetable mechanism mediating the effect of stretch on human myometrium. Design: Myometrial explants, prepared from biopsies obtained at elective caesarean delivery, were either studied acutely, or were maintained in prolonged culture (up to 65 h) under tension with either a 0.6 g or 2.4 g mass, and compared using in vitro contractility, whole genome array, and qRT-PCR. Results: Increased stretch for 24 or 65 h increased potassium-induced and oxytocin-induced contractility. Gene array identified 62 differentially expressed transcripts after 65 h exposure to increased stretch. Two probes for gastrin-releasing peptide (GRP), a known stimulatory agonist of smooth muscle, were among the top five up-regulated by stretch (3.4-fold and 2.0-fold). Up-regulation of GRP by stretch was confirmed in a separate series of 10 samples using qRT-PCR (2.8-fold, P = 0.01). GRP stimulated contractions acutely when added to freshly obtained myometrial strips in 3 out of 9 cases, but Western blot demonstrated expression of the GRP receptor in 9 out of 9 cases. Prolonged incubation of stretched explants in the GRP antagonists PD-176252 or RC-3095 (65 and 24 h respectively) significantly reduced potassium chloride and oxytocin-induced contractility. Conclusion: Stretch of human myometrium increases contractility and stimulates the expression of a known smooth muscle stimulatory agonist, GRP. Incubation of myometrium in GRP receptor antagonists ameliorates the effect of stretch. GRP may be a target for novel therapies to reduce the risk of preterm birth in multiple pregnancy. 9 paired samples of human myometrium cultured under low (0.6g) or high (2.4g) tension
2012-06-14 | E-GEOD-31329 | biostudies-arrayexpress
Project description:Context: Progesterone is important physiologically and therapeutically to maintain uterine quiescence during pregnancy. It acts in part through controlling myometrial gene expression. Objective: To use expression microarray and qRT-PCR validation to determine the changes in gene expression induced by prolonged exposure to a synthetic progestogen. Design: Myometrial explants, obtained at elective Caesarean section (n=9 patients), were maintained in culture, under 0.6g tension, for 3 days in the presence or absence of medroxyprogesterone acetate (MPA, 100nM). Expression array was performed using Illumina human-8 v3 beadchip arrays. Approximately 30% of differentially expressed transcripts were validated in biological replicates (n=10) using qRT-PCR. Results: Transcripts from 114 genes were significantly differentially expressed. These were significantly enriched in inflammatory response (P=0.00001), growth factor activity (P=0.0004) and cytokine activity genes (P=0.008). 34 transcripts were validated using qRT-PCR using an additional independent sample set obtained from 10 further women. There was very close agreement in the fold changes obtained by array and qRT-PCR analysis (r2=0.9, P<0.0001). We confirmed significant down-regulation of a number of genes which have been well characterized as progesterone sensitive, such as IL1B, IL6, PTGS2 and GJA1. However, the top and 6th most down-regulated genes encoded two cytokines, IL11 and IL24, respectively, not previously implicated in mediating the effects of progesterone in myometrium. Both were validated by qRT-PCR (4.3-fold and 2.2-fold down-regulated, both P<0.001). Conclusions: Progestogens control expression of multiple genes in myometrium, including many with no previously recognised role, including IL11 and IL24. It is plausible that proteins encoded by some of these genes may have important, but as yet uncharacterized effects in controlling human parturition. 9 paired samples of human myometrium treated with MPA (10-7M) or vehicle
2011-06-08 | E-GEOD-22961 | biostudies-arrayexpress
Project description:Profiles of genome-wide DNA methylation were investigated in leiomyomas and in myometrium with and without leiomyomas. Profiles of DNA methylation in the myometrium with and without leiomyomas were quite similar while those in leiomyomas were distinct. Bisulphite converted DNA from the three uterine leiomyoma, three myometrium with leiomyoma and three myometrium without leiomyoma were hybridised to the Illumina infinium HumanMethylation450 BeadChip.
2013-09-01 | E-GEOD-45187 | biostudies-arrayexpress
Project description:Estradiol (E2) and relaxin (Rln) are steroid and polypeptide hormones, respectively, with important roles in the female reproductive tract, including myometrium. Some actions of Rln, which are mediated by its membrane receptor RXFP1, require or are augmented by E2 signaling through its cognate nuclear steroid receptor, estrogen receptor alpha (ER⍺). In contrast, other actions of Rln act in opposition to the effects of E2. Here we explore the molecular and genomic mechanisms that underlie the functional interplay between E2 and Rln in the myometrium. We used both ovariectomized female mice and immortalized human myometrial cells expressing wild type or mutant ER⍺ (hTERT-HM-ER⍺ cells). Our results indicate that Rln attenuates the genomic actions and biological effects of estrogen in the myometrium and myometrial cells by reducing phosphorylation ER⍺ on serine 118 (S118). Interestingly, we observed a potent inhibitory effect of Rln on the E2-dependent binding of ER⍺ across the genome. The reduction in ER⍺ binding was associated with changes in the hormone-regulated transcriptome, including a decrease in the E2-dependent expression of neighboring genes. The inhibitory effects of Rln cotreatment on the E2-dependent phosphorylation of ER⍺ required the nuclear dual-specificity phosphatases DUSP1 and DUSP5. Moreover, the inhibitory effects of Rln were reflected in a concomitant inhibition of the E2-dependent contraction of myometrial cells. Collectively, our results identify a pathway that integrates Rln/RXFP1 and E2/ER⍺ signaling, resulting in a convergence of membrane and nuclear signaling pathways to control genomic and biological outcomes.
2024-08-31 | GSE275894 | GEO
Project description:Preterm birth is multifactorial in origin with several distinct clinical phenotypes of differing etiologies, including idiopathic preterm birth. Preterm birth involves the interaction of genetic, societal and environmental factors such as nutrition, lifestyle and stress that may modulate the length of gestation via the epigenome. DNA methylation is a well-studied epigenetic modification whereby promoter methylation commonly represses gene expression and vice versa. Myometrial tissue was obtained at cesarean section at term with or without labor, preterm without labor, idiopathic preterm labor, and twin gestations with labor. Differences in the myometrial epigenomes were identified at gene promoters, CpG islands, CpG island shores and shelves, gene bodies across the genome between the groups of women with preterm labor of different phenotypes vs. normal term labor. Functional clustering analysis indicated the significantly enriched pathways of hypomethylated genes (permissive) were related to acute inflammatory and acute-phase responses. By contrast, genes that are hypermethylated (repressive) revealed enrichment for contractile fibers and cell. This study provides the first high-resolution DNA methylome of human myometrium with evidence for differences in the methylome that may relate to idiopathic preterm birth via regulation of gene expression. The findings extend previous observations that idiopathic preterm labor is associated with subclinical intrauterine infection and inflammatory pathways and point to targets for further molecular characterization of preterm delivery. Comparison of the human myometrial epigenomes in pregnancies with preterm labor of different phenotypes vs. normal term labor
2017-05-04 | E-GEOD-71123 | biostudies-arrayexpress
Project description:Uterine fibroid tissues are often compared to their matched myometrium in an effort to understand their pathophysiology, but it is not clear whether the myometria of uterine fibroid patients represent truly non-disease control tissues. We analyzed the transcriptomes of myometrial samples from non-fibroid patients (M) and from matched myometrial (MF) and fibroid (F) samples to determine whether there is a phenotypic difference between fibroid and non-fibroid myometria. Multidimensional scaling plots revealed that M samples clustered separately from both MF and F samples. A total of 1,169 differentially expressed genes (DEGs) (false discovery rate < 0.05) were observed in the MF comparison with M. Overrepresented Gene Ontology terms showed a high concordance of upregulated gene sets in MF compared to M, particularly extracellular matrix and structure organization. Gene set enrichment analyses showed that the leading-edge genes from the TGFβ signaling and inflammatory response gene sets were significantly enriched in MF. Overall comparison of the three tissues by three-dimensional principal component analyses showed that M, MF, and F samples clustered separately from each other and that a total of 732 DEGs from F vs M were not found in the F vs MF, which are likely understudied in the pathogenesis of uterine fibroids. These results suggest that the transcriptome of MF tissues are different from non-diseased myometrial tissues. Many dysregulated genes were not included in the F vs MF DEGs and may contain key genes for future investigations suggesting that fibroid studies should consider using not only matched myometrium but also non-diseased myometrium as the control.
2021-03-21 | GSE169255 | GEO
Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.
2022-05-05 | GSE202028 | GEO
Project description:The alterations in myometrial biology during labor are not well understood. The myometrium is the contractile portion of the uterus and contributes to labor, a process that may be regulated by the steroid hormone progesterone. Thus, human myometrial tissues from term pregnant in-active-labor (TIL) and term pregnant not-in-labor (TNIL) subjects were used for genome-wide analyses to elucidate potential future preventive or therapeutic targets involved in the regulation of labor. Using myometrial tissues directly subjected to RNA sequencing (RNA-seq), progesterone receptor (PGR) chromatin immunoprecipitation sequencing (ChIP-seq), and histone modification ChIP-seq, we profiled genome-wide changes associated with gene expression in myometrial smooth muscle tissue in vivo. In TIL myometrium, PGR occupied predominatly promoter regions including the classical progesterone response element, whereas it bound predominantly to intergenic regions in TNIL myometrial tissue. Differential binding analysis uncovered over 1700 differential PGR-bound sites between TIL and TNIL with 1361 sites gained and 428 lost in labor. Functional analysis identified multiple pathways involved in cAMP-mediated signaling enriched in labor. A three-way integration of the data for ChIP-seq, RNA-seq and active histone marks uncovered the following genes associated with PGR binding, transcriptional activation and altered mRNA levels: ATP11A, CBX7, and TNS1. In vitro studies showed that ATP11A, CBX7, and TNS1 are progesterone responsive. We speculate that these genes may contribute to the contractile phenotype of the myometrium during various stages of labor. In conclusion, we provide novel labor associated genome-wide events and PGR-target genes that can serve as targets for future mechanistic studies.
2022-05-05 | GSE202027 | GEO
Project description:To compare gene expression in human myometrium after TSA treatment to gene expression after treatment with a specific HDAC8 inhibitor Four Control, four TSA and four Compound 2 samples (2 patients, replicated) derived from non-pregnant myometrial strips
2012-02-07 | E-GEOD-27124 | biostudies-arrayexpress