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复发性种植失败中与子宫内膜容受性受损相关的基于miRNA和mRNA的容受性阶段之间的不同步

Asynchrony Between Endometrial miRNA- and mRNA-Based Receptivity Stages Associated with Impaired Receptivity in Recurrent Implantation Failure.

作者信息

Lee Yu-Jen, Lee Chi-Ying, Cheng En-Hui, Chen Wei-Ming, Yang Pok Eric, Lee Chun-I, Lee Tsung-Hsien, Lee Maw-Sheng

机构信息

Genetic Diagnosis Laboratory, Lee Women's Hospital, Taichung 40652, Taiwan.

Department of Post-Baccalaureate Medicine, National Chung Hsing University, Taichung 40227, Taiwan.

出版信息

Int J Mol Sci. 2025 Jul 30;26(15):7349. doi: 10.3390/ijms26157349.

DOI:10.3390/ijms26157349
PMID:40806480
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347538/
Abstract

Understanding the molecular basis of endometrial receptivity is crucial for improving implantation outcomes in assisted reproduction, especially for patients with recurrent implantation failure (RIF). This study investigates the timing relationship between microRNA (miRNA) and messenger RNA (mRNA) profiles in the endometrium using simultaneously the endometrial receptivity array (ERA) and the microRNA receptivity assay (MIRA) in 100 RIF patients undergoing euploid blastocyst transfer. The concordance rate between ERA and MIRA was 72% (Kappa = 0.50), suggesting partial overlap in profiling. Patients were stratified by the timing sequence of miRNA relative to mRNA into Fast, Equal, and Slow groups. Those with delayed miRNA expression (Slow group) had significantly lower pregnancy rates (54.5%) than those with synchronous or leading miRNA expression (81.9% and 94.1%, respectively; = 0.031). Moreover, the Slow group exhibited higher prior implantation failure counts and altered expression in 15 miRNAs, many involved in aging-related pathways. These findings highlight that asynchronous miRNA-mRNA profiles may reflect impaired receptivity and suggest that miRNA-based staging adds valuable diagnostic insight beyond mRNA profiling alone. Dual assessment of mRNA and miRNA profiles may offer additional diagnostic insight into endometrial receptivity but requires further validation before clinical application.

摘要

了解子宫内膜容受性的分子基础对于改善辅助生殖中的着床结局至关重要,尤其是对于反复着床失败(RIF)的患者。本研究在100例接受整倍体囊胚移植的RIF患者中,同时使用子宫内膜容受性阵列(ERA)和微小RNA容受性检测(MIRA),研究子宫内膜中微小RNA(miRNA)和信使核糖核酸(mRNA)谱之间的时间关系。ERA和MIRA之间的一致性率为72%(Kappa = 0.50),表明在谱分析中有部分重叠。根据miRNA相对于mRNA的时间顺序,将患者分为快速组、相等组和缓慢组。miRNA表达延迟的患者(缓慢组)的妊娠率(54.5%)显著低于miRNA表达同步或领先的患者(分别为81.9%和94.1%;P = 0.031)。此外,缓慢组表现出更高的既往着床失败次数,并且15种miRNA的表达发生改变,其中许多涉及衰老相关途径。这些发现突出表明,miRNA-mRNA谱的不同步可能反映容受性受损,并表明基于miRNA的分期除了单独的mRNA谱分析之外还增加了有价值的诊断见解。对mRNA和miRNA谱的双重评估可能为子宫内膜容受性提供额外的诊断见解,但在临床应用前需要进一步验证。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a263/12347538/0bb4d3a5bee9/ijms-26-07349-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a263/12347538/df6d28e05cb8/ijms-26-07349-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a263/12347538/0bb4d3a5bee9/ijms-26-07349-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a263/12347538/df6d28e05cb8/ijms-26-07349-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a263/12347538/0bb4d3a5bee9/ijms-26-07349-g002.jpg

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本文引用的文献

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Biomedicines. 2025 May 13;13(5):1189. doi: 10.3390/biomedicines13051189.
2
When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation.当胚胎遇见子宫内膜:鉴定胚胎着床成功所需的特征。
Int J Mol Sci. 2024 Feb 29;25(5):2834. doi: 10.3390/ijms25052834.
3
Bioinformatic analysis of endometrial miRNA expression profile at day 26-28 of pregnancy in the mare.
妊娠第 26-28 天母马子宫内膜 miRNA 表达谱的生物信息学分析。
Sci Rep. 2024 Feb 16;14(1):3900. doi: 10.1038/s41598-024-53499-x.
4
MicroRNAs in Endometriosis: Insights into Inflammation and Progesterone Resistance.子宫内膜异位症中的微小RNA:对炎症和孕激素抵抗的见解
Int J Mol Sci. 2023 Oct 9;24(19):15001. doi: 10.3390/ijms241915001.
5
Human blastocysts uptake extracellular vesicles secreted by endometrial cells containing miRNAs related to implantation.人类囊胚摄取由子宫内膜细胞分泌的含有与着床相关的 miRNAs 的细胞外囊泡。
Hum Reprod. 2023 Aug 1;38(8):1547-1559. doi: 10.1093/humrep/dead138.
6
ESHRE good practice recommendations on recurrent implantation failure.欧洲人类生殖与胚胎学会关于反复种植失败的良好实践建议。
Hum Reprod Open. 2023 Jun 15;2023(3):hoad023. doi: 10.1093/hropen/hoad023. eCollection 2023.
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Review of Endometrial Receptivity Array: A Personalized Approach to Embryo Transfer and Its Clinical Applications.子宫内膜容受性阵列综述:胚胎移植的个性化方法及其临床应用
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