Project description:The maintenance of coordinated powerful episodic contractions of the uterus is the crucial factor for normal labor. The uterine contractility is gradually enhanced with the progression of labor, which is related to the gene expression of myometrium, competing endogenous RNA (ceRNA) can also regulate the gene expression. To better understand the role of ceRNA network in labor, transcriptome sequencing was performed on the myometrium of 17 parturients at different labor duration. Furthermore, an correlated analysis was performed to identify mRNA, long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) which correlated with their expression levels and labor duration. Then, targeting relationships between mRNAs, lncRNAs, circRNAs and miRNAs were predicted, and the ceRNA regulatory network was established.This analysis identified 934 RNAs positively correlated with labor duration (859 mRNAs, 28 lncRNAs, 45 circRNAs, and 2 miRNAs) and 153 RNAs negatively correlated with labor duration (122 mRNAs, 28 lncRNAs, and 3 miRNAs).
Project description:Proteome data from 20 myometrium (in labor, IL, n = 10; non-labor, NL, n = 10) was performed by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS).
Project description:The maintenance of coordinated powerful episodic contractions of the uterus is the crucial factor for normal labor. The uterine contractility is gradually enhanced with the progression of labor, which is related to the gene expression of myometrium, competing endogenous RNA (ceRNA) can also regulate the gene expression. To better understand the role of ceRNA network in labor, transcriptome sequencing was performed on the myometrium of 17 parturients at different labor duration. Furthermore, an correlated analysis was performed to identify mRNA, long non-coding RNA (lncRNA), circular RNA (circRNA), and microRNA (miRNA) which correlated with their expression levels and labor duration. Then, targeting relationships between mRNAs, lncRNAs, circRNAs and miRNAs were predicted, and the ceRNA regulatory network was established.This analysis identified 934 RNAs positively correlated with labor duration (859 mRNAs, 28 lncRNAs, 45 circRNAs, and 2 miRNAs) and 153 RNAs negatively correlated with labor duration (122 mRNAs, 28 lncRNAs, and 3 miRNAs).
Project description:Labor involves a variety of coordinated events across physiological and biochemical aspects, the molecular mechanism responsible for the transition of the myometrium from the quiescent to a contractile state remains indistinct.The global transcriptome in human non-labor and in labor myometrium was investigated through RNA sequencing (RNA-seq) to explore biological processes and pathways alterations during labor. The transcriptomic bioinformatics results showed that the up-regulated mRNAs increased inflammation under hypoxia stress in laboring myometrium.
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.
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.
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. Currently there is no treatment that can prevent or block preterm labor. In order to identify the molecular regulators of preterm spontaneous labor in the human myometrium, we studied the gene expression profiles of samples with Preterm Spontaneous Labour (PSL) and compared them with the gene expression profiles of samples with Preterm No Labor (PNL).
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