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免疫分析和 RNA 测序揭示部分不明原因反复着床失败的原因。

Immune profiling and RNA-seq uncover the cause of partial unexplained recurrent implantation failure.

机构信息

An Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University Changsha, China; Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China.

Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China; Clinical Research Center For Reproduction and Genetics In Hunan Province, China.

出版信息

Int Immunopharmacol. 2023 Aug;121:110513. doi: 10.1016/j.intimp.2023.110513. Epub 2023 Jun 18.

DOI:10.1016/j.intimp.2023.110513
PMID:37336073
Abstract

BACKGROUND

Detailed knowledge of the changes in endometrial immune cells during the window of implantation in unexplained recurrent implantation failure (RIF) patients, the functions performed by immune cells, and the interactions between them is largely lacking. This study aimed to classify RIF patients and explore the mechanism through endometrial immune profiling and RNA-seq analysis.

METHODS

This study enrolled a total of 172 patients, comprising 144 women with unexplained RIF and 28 fertile women. Endometrial samples were collected using endometrial scratching at the mid-luteal phase before in vitro fertilization treatment or pregnancy. Transcriptome sequencing and immunohistochemical staining of endometrial immune cells including natural killer (NK) cells, macrophages, T cells, and B cells were performed.

MAIN OUTCOME MEASURE(S): Comparison of the percentage of endometrial immune cells and the RNA-seq information between RIF patients and fertile control patients.

RESULT(S): The proportions of uterine CD56 uNK cells, CD57 NKT cells, CD68 macrophages, and CD19 B cells were significantly elevated in RIF patients. In addition, the number of positive CD68 glandular lumens was significantly higher in RIF patients than in the fertile group. In addition, based on this result, we classified RIF patients into three categories.

CONCLUSION(S): Hyperactivation of endometrial immune cells may be associated with reduced endometrial tolerance and recurrent implantation failure, affecting pregnancy outcomes in RIF patients.

摘要

背景

对于不明原因的反复着床失败(RIF)患者,着床窗期间子宫内膜免疫细胞的变化、免疫细胞的功能及其相互作用的详细知识在很大程度上尚未可知。本研究旨在通过子宫内膜免疫谱分析和 RNA-seq 分析对 RIF 患者进行分类,并探讨其机制。

方法

本研究共纳入 172 例患者,包括 144 例不明原因的 RIF 患者和 28 例生育力正常的妇女。在体外受精治疗或妊娠前的黄体中期,通过子宫内膜刮除术采集子宫内膜样本。对包括自然杀伤(NK)细胞、巨噬细胞、T 细胞和 B 细胞在内的子宫内膜免疫细胞进行转录组测序和免疫组织化学染色。

主要观察指标

RIF 患者和生育力正常对照组患者子宫内膜免疫细胞比例和 RNA-seq 信息的比较。

结果

RIF 患者子宫内 CD56 uNK 细胞、CD57 NKT 细胞、CD68 巨噬细胞和 CD19 B 细胞的比例显著升高。此外,RIF 患者的 CD68 阳性腺腔数量明显高于生育组。此外,基于这一结果,我们将 RIF 患者分为三类。

结论

子宫内膜免疫细胞的过度激活可能与子宫内膜容受性降低和反复着床失败有关,从而影响 RIF 患者的妊娠结局。

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Int Immunopharmacol. 2023 Aug;121:110513. doi: 10.1016/j.intimp.2023.110513. Epub 2023 Jun 18.
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