JunD cistrome of the human myometrium at during term pregnancy and labour
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE240816 | GEO | 2025/03/18
REPOSITORIES: GEO
Similar Datasets
Project description:JunD cistrome of the human myometrium at during term pregnancy and labour
| PRJNA1005306 | ENA
Project description:We have generated genome-wide binding and expression datasets in uterine smooth muscle (myometrium) from murine models of pregnancy and labour. ChIP-seq and total RNA-seq experiments were conducted to evaluate changes in the genomic and transcriptomic landscape of the myometrium prior to, during, and after labour onset.
2020-07-10 | GSE124295 | GEO
Project description:We have generated transcriptomic datasets of the human uterine smooth muscle (myometrium) tissue. RNA-seq experiments were conducted to evaluate gene expression changes that occur as the uterus transitions from pregnancy to labour using human myometrium tissue.
2025-03-18 | GSE244863 | 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:Preterm birth is the leading cause of infant morbidity and mortality. There has been interest in developing prostaglandin F2α (PGF2α) antagonists as a new treatment for preterm birth although much of the rationale for their use is based on studies in rodents where PGF2α initiates labour by regressing the corpus luteum and reducing systemic progesterone concentrations. How PGF2α antagonism would act in humans that do not have a fall in systemic progesterone remains unclear. One possibility, in addition to an acute stimulation of contractions, is a direct alteration of the myometrial smooth muscle cell state towards a pro-labour phenotype. In this study we developed an immortalised myometrial cell line, MYLA, derived from myometrial tissue obtained from a pregnant, non‐labouring patient as well as a novel class of PGF2α receptor (FP) antagonist. We verified the functionality of the cell line by stimulation with PGF2α, which resulted in Gαq specific coupling and Ca2+ release that were inhibited by FP antagonism. Compared to four published FP receptor antagonists, the novel FP antagonist N582707 was the most potent compound (Fmax 7.67 ± 0.63 (IC50 21.26 nM), AUC 7.30 ± 0.32 (IC50 50.43 nM) and frequency of Ca2+ oscillations 7.66 ± 0.41 (IC50 22.15 nM)). RNA‐sequencing of the MYLA cell line at 1, 3, 6, 12, 24 & 48 hours post PGF2α treatment revealed a transforming phenotype from a fibroblastic to smooth muscle mRNA profile. PGF2α treatment increased expression of MYLK, CALD1 and CNN1 as well as the pro-labour genes OXTR, IL6 and IL11 which were inhibited by FP antagonism. Concomitant with inhibition of a smooth muscle, pro-labour transition, FP antagonism increased the expression of the fibroblast marker genes DCN, FBLN1 and PDGFRA. Our findings suggest that in addition to the well described acute contractile effect, PGF2α transforms myometrial smooth muscle cells from a myofibroblast to smooth muscle, pro-labour like state, and that the novel compound N582707 has potential for prophylactic use in preterm labour management beyond its use as an acute tocolytic drug.
2023-12-13 | GSE249529 | 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.
2012-06-15 | GSE31329 | GEO
Project description:Purpose: To chart the human myometrial transcriptomes before and after the onset of labour. Methods: Tophat splice junction mapping of paired-end reads, HTSeq to generate counts, cufflinks to track transcripts, DESeq, edgeR and baySeq to detect differentially expressed genes and principal component analysis for clustering analyses. Results: We mapped on average 14 million paired-end reads per sample (counting each end individually) to the human genome (build hg19) and covered the expressed transcriptome about 13 times with a TopHat-HTSeq workflow. We performed a comparative analysis with an analogous microarray study (Mittal et al., 2010) and found some overlap between the RNA-seq and the microarray data. Conclusions: Our study is the first RNA-seq study of the human myometrium before and after the onset of labour. We show that while microarray and RNA-seq studies may complement each other, RNA-seq has a much greater resolution. At term with and at term without labour human myometrial mRNA profiles were generated by deep sequencing, using Illumina GAIIx (five biological replicates each).
2014-02-17 | E-GEOD-50599 | biostudies-arrayexpress
Project description:Purpose: To chart the human myometrial transcriptomes before and after the onset of labour. Methods: Tophat splice junction mapping of paired-end reads, HTSeq to generate counts, cufflinks to track transcripts, DESeq, edgeR and baySeq to detect differentially expressed genes and principal component analysis for clustering analyses. Results: We mapped on average 14 million paired-end reads per sample (counting each end individually) to the human genome (build hg19) and covered the expressed transcriptome about 13 times with a TopHat-HTSeq workflow. We performed a comparative analysis with an analogous microarray study (Mittal et al., 2010) and found some overlap between the RNA-seq and the microarray data. Conclusions: Our study is the first RNA-seq study of the human myometrium before and after the onset of labour. We show that while microarray and RNA-seq studies may complement each other, RNA-seq has a much greater resolution.
2014-02-17 | GSE50599 | GEO
Project description:Infiltration of human myometrium and cervix with leukocytes and formation of a pro-inflammatory environment within the uterus has been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labour. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines including: Interleukin-1beta (IL1B), chemokine C-C motif ligand 3 (CCL3) and Colony Stimulating Factor 3 (CSF3). We additionally demonstrate that PROK1 increases expression of chemokines C-C motif ligand 20 (CCL20), Interleukin-6 (IL-6), Interleukin-8 (IL-8), prostaglandin synthase 2 (PTGS2) and prostaglandin E2 and F2? secretion. We propose that PROK1 is a novel inflammatory mediator that can contribute to onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection. Total RNA was extracted from human term non-labour myometrium explants treated with prokineticin for 6 and 24 hours compared to vehicle-treated explants. Six biological replicates were analyzed for each treatment and time point. Two of the 6-hour vehicle samples failed a quality-control analysis and were substituted with a 4-hour vehicle treatment from the same tissue sample in each case.
2011-12-31 | E-GEOD-28272 | biostudies-arrayexpress
Project description:Infiltration of human myometrium and cervix with leukocytes and formation of a pro-inflammatory environment within the uterus has been associated with the initiation of both term and preterm parturition. The mechanism regulating the onset of this pro-inflammatory cascade is not fully elucidated. We demonstrate that prokineticin 1 (PROK1) is up-regulated in human myometrium and placenta during labour. Gene array analysis identified 65 genes up-regulated by PROK1 in human myometrium, mainly cytokines and chemokines including: Interleukin-1beta (IL1B), chemokine C-C motif ligand 3 (CCL3) and Colony Stimulating Factor 3 (CSF3). We additionally demonstrate that PROK1 increases expression of chemokines C-C motif ligand 20 (CCL20), Interleukin-6 (IL-6), Interleukin-8 (IL-8), prostaglandin synthase 2 (PTGS2) and prostaglandin E2 and F2α secretion. We propose that PROK1 is a novel inflammatory mediator that can contribute to onset of human parturition at term and partially mediate premature onset of inflammatory pathways during bacterial infection.
2011-12-31 | GSE28272 | GEO