Genome Scale Analysis of miRNA and mRNA regulation during preterm labor
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA378795 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5335880_1.fastq.gz | Fastqsanger.gz | |||
| SRR5335880_2.fastq.gz | Fastqsanger.gz | |||
| SRR5335890_1.fastq.gz | Fastqsanger.gz | |||
| SRR5335890_2.fastq.gz | Fastqsanger.gz | |||
| SRR5335900_1.fastq.gz | Fastqsanger.gz |
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Project description:The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL.
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Project description:The goal of this study was to define relationships between peripheral blood miRNAs and mRNAs of women undergoing idiopathic preterm labor (PTL) and compare network level changes to control women that deliver at term.Using RNA Sequencing we have performed global miRNA and mRNA profiling in both monocytes and whole blood leukocytes of women who underwent PTL (N=15) matched to non-pathological controls (N=30) as a part of the Ontario Birth Study cohort. We have identified differentially expressed miRNAs, mRNAs and pathways associated with PTL. Intriguingly, we found perturbations in many cellular signaling pathways, particularly in interleukin signaling. We also predicted mRNA targets for specific miRNAs and used these predictions to build putative miRNA-mRNA networks. We identified 6 miRNAs significantly associated with PTL whose expression is negatively correlated with expression of 14 predicted mRNA targets that are also significantly associated with PTL.
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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
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Project description:Distinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens. Keywords: myometrial gene expression, preterm versus term labor
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