The mice uterine gene expression landscape from early to late pregnancy
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE85934 | GEO | 2018/11/07
REPOSITORIES: GEO
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Project description:Preterm birth, defined as delivery before the 37th week of gestation, is the most common cause of neonatal mortality and the second leading cause of death in children under five years of age. Preterm birth is associated with immediate and long term morbidity as well as growth and developmental delay. The lack of access to human myometrial samples during ongoing uncomplicated pregnancy seriously hampers proper understanding of the sequence of events leading to parturition initiation. In our previous work we used mouse as a model and profiled gene expression in mouse uterus from early E6.5 to late gestation E17.5. We identified Tbx2 as one of the putative upstream regulators during mid-gestation (E10.5, E12.5, E15.5). The role of TBX2 in human myometrium has not been investigated. In this study we identify the gene targets of TBX2 by overexpressing TBX2 in cultured telomerase immortalised myometrial cells followed by gene expression profiling using microarrays.
2021-04-29 | GSE134446 | GEO
Project description:Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a non-contractile state until term and then surmounts this state to enter labor. Here, we show in mice that dynamic deposition and removal of repressive H3K27me3 chromatin marks in decidual stromal cells dictate both elements of pregnancy success. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets insures uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and, most unexpectedly, generating myofibroblasts and associated wound healing responses. In late gestation, genome-wide H3K27 demethylation allows for target gene upregulation, decidual activation, and labor entry. Strikingly, pharmacological inhibition of this latter process not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a non-inflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders.
2017-10-23 | GSE105455 | GEO
Project description:Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a non-contractile state until term and then surmounts this state to enter labor. Here, we show in mice that dynamic deposition and removal of repressive H3K27me3 chromatin marks in decidual stromal cells dictate both elements of pregnancy success. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets insures uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and, most unexpectedly, generating myofibroblasts and associated wound healing responses. In late gestation, genome-wide H3K27 demethylation allows for target gene upregulation, decidual activation, and labor entry. Strikingly, pharmacological inhibition of this latter process not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a non-inflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders.
2017-10-23 | GSE105444 | GEO
Project description:Uterine contractile dysfunction leads to pregnancy complications such as preterm birth and labor dystocia. Progesterone is necessary to suppress uterine contractions to prevent premature labor. As humans maintain high levels of progesterone throughout parturition, a functional progesterone withdrawal hypothesis suggests that relative levels of myometrial progesterone receptor isoforms PGR-A and PGR-B switch at parturition, where PGR-B promotes a relaxed state and PGR-A result in increased uterine contractility. Our objective is to determine the effects of altered levels of PGR-B and PGR-A in the mouse myometrium on pregnancy and parturition using transgenic mouse models in which the relative levels of these isoforms are altered specifically in the myometrium. Overexpression of PGR-B is associated with a markedly increased gestational length compared to control mice. In both ex vivo and in vivo experiments, myometrium of PGR-B overexpressing mice have prolonged labor, a significant decrease in uterine contractility, and a high incidence of labor dystocia. Conversely, overexpression of PGR-A is associated with an increase in uterine contractility without a change in gestational length. Uterine RNAseq at mid-pregnancy identified isoform-specific downstream targets and genes that were commonly regulated by both PGR isoforms. Gene signature analyses further revealed that PGR-B promotes muscle relaxation and that PGR-A is pro-inflammation. High levels of PGR-B manifest a genetic profile of a blunted phospholipase C pathway that mediates oxytocin and angiotensin II induced muscle contraction. These findings provided in vivo support that PGR isoform levels determine distinct transcriptomic landscapes and pathways in myometrial function and labor.
2021-02-24 | GSE146634 | GEO
Project description:We quantified the targets and kinetics of DNA methylation acquisition in mouse embryos, and determined the contribution of the de novo methyltransferases DNMT3A and DNMT3B to this process. We provide single-base maps of cytosine methylation by RRBS from the blastocysts to post-implantation stages and in embryos lacking DNMT3A or DNMT3B activity, and performed RNA-Seq in embryos lacking DNMT3B activity. We sequenced RRBS libraries prepared from genomic DNA isolated from embryos at consecutive stages of development between E3.5 and E11.5,and adult differentiated cells (sperm, liver). We performed RRBS on blastocysts at E3.5/E4.5, dissected epiblasts at E5.5/E6.5/E7/5, whole embryos at E8.5/E10.5 and limbs at E11.5. RRBS experiments in Dnmt3a-/- and Dnmt3b-/- embryos were performed in biological duplicates on individual embryos. We sequenced RNA-Seq libraries prepared from total RNAs of three WT and Dnmt3b-/- littermate embryos collected at E8.5.
2014-11-14 | E-GEOD-60334 | biostudies-arrayexpress
Project description:Amnion is a vital structure for human parturition, and it is anatomically compartmentalized into the placental amnion and the reflected amnion. microRNA expression was profiled to determine the expression pattern and its significance in the placental amnion and the reflected amnion in association with spontaneous labor at term. placental and reflected amnion tissue from two groups of women (term in labor and term no labor)
2011-08-31 | E-GEOD-27441 | biostudies-arrayexpress
Project description:The goal of this study was to examine genetic networks that control endocrine cell type specification and differentiation. RNA-Seq technology was used to explore the gene expression profiles of pancreatic endocrine progenitor cells (at E10.5 and E15.5), impaired endocrine progenitor cells (at E10.5 and E15.5), and pre-beta cells (at E15.5) in mouse.
2015-01-26 | E-MTAB-3272 | biostudies-arrayexpress
Project description:We report gene expression patterns in embryonic mice (E8.5, E9.5, E10.5) through RNA-seq of 13 tissue/stage combinations in order to generage an atlas of early mouse craniofacial gene expression. Embryos at E8.5, E9.5, and E10.5 CD1 were collected from CD1 mice, fom multiple micro-regions whose development, differentiation and signaling are responsible for the construction of the mammalian face.
2014-03-18 | E-GEOD-55966 | biostudies-arrayexpress
Project description:Introduction: Disruption in the synergistic machinery of human parturition can cascade into an ill-timed onset of labor, jeopardizing pregnancy outcomes and contributing to perinatal morbidity and mortality. Parturition is invoked by a phenotypic shift towards a pro-inflammatory predominant state; however, the mechanistic underpinnings as well as tissue-specific role and pathophysiological implications remain elusive. Predicting labor trajectory is further hindered due to confounding by concurrent processes either unrelated or exclusive to advancing gestation. It is thus critical to employ a strategic plan when probing the genetic and environmental tug-of-war that underlies parturition. Methods: We collected human deciduas to explore the genetic control of inflammation within the immunologically-distinct part of the placenta. We performed a genome-wide profiling of the trascriptome to incorporate environmental and fetal stimuli effects on phenotypic divergence. Samples were segregated into term labor (n=16), premature labor (n=16), and nonlaboring C-section (n=18) to distinguish between factors governing gestation duration and those involved in the final pathway of labor. Leveraging the high resolution of next-generation sequencing, we analyzed gene-, isoform-, and network scale-level variability across labor states and then interrogated clinical traits to extract key players in labor timing and development. Results: All samples exhibited a global upregulated expression of adhesion, vascular, humoral, and endocrine genes enriched in the placenta and critical to pregnancy sustenance. Nonlaboring deciduas revealed the most divergent transcriptional landscape, with significant enrichment for dysregulated vacular extracellular matrix remodeling and muscle contractility. Premature deciduas showed a more prominent immune-mediated fetal rejection, infection response, and lipid metabolism signature. Conclusion: Our study provides a comprehensive steady-state snapshot of co-/post-transcriptional changes across various modes of parturition. Using multilayered analytics, it suggests the withdrawal of immune suppression at the maternal-fetal interface during labor development, a process that is further enhanced with pre-existing intrauterine infection and systemic stress to potentially modulate labor timing.
2023-05-01 | GSE140602 | GEO
Project description:Single-cell RNA-Seq RNA from medial ganglionic eminence at E11.5, E13.5, E15.5 or E17.5. The ID of this project in Genentech's ExpressionPlot database is PRJ0007389
2017-03-02 | GSE94641 | GEO