Dataset Information

MicroRNA regulation of cyclooxygenase-2 during embryo implantation.

ABSTRACT: The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. Because microRNAs (miRNAs) have major roles in regulating gene expression, we speculated that they participate in directing the highly regulated spatiotemporally expressed genetic network during implantation. Here, we show that two miRNAs, mmu-miR-101a and mmu-miR-199a*, are spatiotemporally expressed in the mouse uterus during implantation coincident with expression of cyclooxygenase-2, a gene critical for implantation. More interestingly, our in vitro gain- and loss-of-function experiments show that cyclooxygenase-2 expression is posttranscriptionally regulated by these two miRNAs. We report on miRNA-mediated regulation of uterine gene expression in the context of implantation. We believe that many other critical genes related to this process are also regulated by miRNAs. Thus, elucidating the physiological roles of uterine miRNAs will help us better understand the genetic control of implantation, the gateway to a successful pregnancy.

SUBMITTER: Chakrabarty A

PROVIDER: S-EPMC1986627 | biostudies-literature | 2007 Sep

REPOSITORIES: biostudies-literature

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MicroRNA regulation of cyclooxygenase-2 during embryo implantation.

Chakrabarty Anindita A Tranguch Susanne S Daikoku Takiko T Jensen Kevin K Furneaux Henry H Dey Sudhansu K SK

Proceedings of the National Academy of Sciences of the United States of America 20070911 38

The implantation process is complex, requiring reciprocal interactions between implantation-competent blastocysts and the receptive uterus. Because microRNAs (miRNAs) have major roles in regulating gene expression, we speculated that they participate in directing the highly regulated spatiotemporally expressed genetic network during implantation. Here, we show that two miRNAs, mmu-miR-101a and mmu-miR-199a*, are spatiotemporally expressed in the mouse uterus during implantation coincident with e ...[more]

PMID: 17848513

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Project description:BackgroundMicroRNAs (miRNAs) are small, non-coding RNAs that are dysregulated in many diseases and can act as biomarkers. Although well-studied in cancer, the role of miRNAs in embryo implantation is poorly understood. Approximately 70% of embryos fail to implant following in-vitro fertilization and embryo transfer, 10% of patients experienced recurrent implantation failure. However, there are no well-established biomarkers that can predict implantation failure. Our purpose is to investigate distinct miRNA profiles in plasma and plasma exosomes during the window of implantation between patients with failed implantation and successful implantation.MethodsWe select a nested case-control population of 12 patients with implantation failure or successfully clinical pregnancy using propensity score matching. RNA was extracted from plasma and plasma exosomes collected during the window of implantation (WOI). MicroRNA expression in all samples was quantified using microRNA sequencing. The intersection of differently expressed miRNAs in plasma and exosomes were further validated in the GEO dataset. Significantly altered microRNAs in both plasma and plasma exosomes were then subjected to target prediction and KEGG pathway enrichment analyses to search for key signaling pathways. WGCNA analysis was performed to identify hub miRNAs associated with implantation.Results13 miRNAs were differentially expressed in both plasma and plasma exosomes in patients with implantation failure. Among them, miR-150-5p, miR-150-3p, miR-149-5p, and miR-146b-3p had consistent direction changes in endometrium of patients with recurrent implantation failure (RIF), miR-342-3p had consistent direction changes in blood samples of patients with RIF. Pathway enrichment analysis showed that the target genes of differentially expressed miRNAs are enriched in pathways related to embryo implantation. WGCNA analysis indicated that miR-150-5p, miR-150-3p, miR-146b-3p, and miR-342-3p are hub miRNAs.ConclusionsImplantation failure is associated with distinct miRNA profiles in plasma and plasma exosomes during WOI.

Dataset Information

MicroRNA regulation of cyclooxygenase-2 during embryo implantation.

Publications

MicroRNA regulation of cyclooxygenase-2 during embryo implantation.

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