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The dynamic change of microRNA expression profile in endometrium and peripheral blood during the peri-implantation window

ABSTRACT: Previous studies have shown that microRNAs (miRNAs) play a crucial role in human embryo implantation by regulating the expression of genes involved in the process. While dynamic changes in plasma miRNA during the peri-implantation period have been established, systematic and comprehensive studies on miRNA expression changes in both endometrial tissue and blood during this period are lacking. A total of 62 subjects, including 62 endometrial tissue samples and 62 paired peripheral blood samples, were collected from participants undergoing hormone treatment cycles between day P+3 to P+7. Next-generation sequencing (NGS) assay was used to profile miRNA expression levels, and the results were annotated using miRBase. To identify the dynamic differentially expressed (DE) miRNAs between day P+3 to P+7, we compared the following group pairs: P+3 and P+4, P+4 and P+5, P+5 and P+6, and P+6 and P+7. We then perform functional miRNA-target interaction (MTI) and pathway enrichment analyses to understand the biological functions of dynamic DE miRNAs. We identified 76 and 48 dynamic DE miRNAs in endometrial tissue and peripheral blood samples, respectively. Functional MTI and pathway enrichment analyses revealed that these DE miRNAs influence numerous biological pathways and functions related to implantation, such as cell senescence, cell growth, apoptosis, focal adhesion, autophagy, platelet activation and signaling. Although only 10 DE miRNAs overlapped between endometrial tissue and peripheral blood, 7 of these showed consistent dynamic expression changes. Further analysis revealed a high similarity in the biological pathways and functions involving the target genes of DE miRNAs in both endometrial tissue and peripheral blood. 76 and 48 dynamic DE miRNAs were identified in endometrial tissue and peripheral blood samples, respectively. These miRNAs influence numerous biological pathways and functions related to implantation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE297808 | GEO | 2025/05/22

REPOSITORIES: GEO

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Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.

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The dynamic change of microRNA expression profile in endometrium and peripheral blood during the peri-implantation window

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