在体外受精和胚胎移植后着床失败的窗口期，血浆和血浆外泌体中的 microRNA 特征。
MicroRNA signatures in plasma and plasma exosome during window of implantation for implantation failure following in-vitro fertilization and embryo transfer.
机构信息
Department of Gynecology and Obstetrics, NanFang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Department of Reproductive Medicine Center, Foshan Maternal and Child Health Care Hospital, Southern Medical University, Foshan, 528000, Guangdong, China.
出版信息
Reprod Biol Endocrinol. 2021 Dec 7;19(1):180. doi: 10.1186/s12958-021-00855-5.
BACKGROUND
MicroRNAs (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.
METHODS
We 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.
RESULTS
13 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.
CONCLUSIONS
Implantation failure is associated with distinct miRNA profiles in plasma and plasma exosomes during WOI.
背景
微小 RNA（miRNA）是一种小的非编码 RNA，在许多疾病中失调，可作为生物标志物。虽然 miRNA 在癌症中研究较多，但在胚胎植入中的作用知之甚少。大约 70%的胚胎在体外受精和胚胎移植后未能着床，10%的患者经历反复着床失败。然而，目前尚无可靠的生物标志物可预测着床失败。我们的目的是在着床窗口期，研究着床失败和成功妊娠患者的血浆和血浆外泌体中不同的 miRNA 图谱。
方法
我们选择了 12 名着床失败或成功临床妊娠的患者进行嵌套病例对照研究，采用倾向评分匹配。在着床窗口期（WOI）采集血浆和血浆外泌体，提取 RNA。使用 miRNA 测序定量分析所有样本中的 miRNA 表达。进一步在 GEO 数据集验证血浆和外泌体中差异表达的 miRNA 交集。对血浆和外泌体中均显著改变的 microRNA 进行靶基因预测和 KEGG 通路富集分析，寻找关键信号通路。进行 WGCNA 分析，鉴定与着床相关的 hub miRNAs。
结果
在着床失败患者的血浆和血浆外泌体中，有 13 个 miRNA 表达差异。其中 miR-150-5p、miR-150-3p、miR-149-5p 和 miR-146b-3p 在复发性着床失败（RIF）患者的子宫内膜中具有一致的变化方向，miR-342-3p 在 RIF 患者的血液样本中具有一致的变化方向。通路富集分析表明，差异表达 miRNA 的靶基因富集在与胚胎着床相关的通路中。WGCNA 分析表明 miR-150-5p、miR-150-3p、miR-146b-3p 和 miR-342-3p 是 hub miRNAs。
结论
着床失败与 WOI 期间血浆和血浆外泌体中不同的 miRNA 图谱有关。
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