Exploring Therapeutic Targets and Drugs for Recurrent Spontaneous Abortion by M1 Macrophage Exosome Sequencing Analysis: A Bioinformatic and Vitro Study

IF 2.4 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology Pub Date : 2025-06-19 DOI:10.1111/aji.70115

Cen Tang, Wanqin Hu, Yunhua Liu

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引用次数: 0

Abstract

Problem

Recurrent spontaneous abortion (RSA) is defined as two or more consecutive spontaneous abortions in the first 24 weeks of pregnancy. However, the detailed molecular mechanisms behind RSA remain unclear.

Method of Study

We used bioinformatics and systems biology approaches to analyze the underlying molecular mechanisms to provide new insights into the biology of M1 macrophage exosome differentially expressed genes (DEGs) in RSA patients and to identify potential drugs to treat RSA. The trophoblast (HTR-8) was co-cultured with the M1 macrophage exosomes induced by THP-1, and the cell model was constructed for transcriptome sequencing analysis and data source construction. Functional enrichment and pathway analysis of DEGs among the three groups were performed. In addition, differential expression of key genes was verified by RT-qPCR.

Results

We obtained 172 DEGs from the sequencing data. Metabolic and immune-related pathways and functions are the main pathways of its enrichment. FOCX1, GATA2, YY1, TFAP2A, MEFF2A, and STAT3 are the major transcription factors (TFs) of M1 macrophage exosomes in RSA. Hsa-mir-106b-5p, hsa-mir-149-3p, and hsa-mir-520a-3p are associated with RSA. Finally, the DEGS-disease and DEGS-drug interaction networks are predicted. Gene Ontology (GO) and Kyoto Genome Encyclopedia (KEGG) enrichment analysis revealed clusters and targets associated with maternal and fetal interface immune tolerance in RSA M1 macrophage exosomes.

Conclusions

The candidate targets and drugs obtained from M1-type macrophage exosomes in this study may contribute to the effective treatment of RSA.

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通过M1巨噬细胞外泌体测序分析探索复发性自然流产的治疗靶点和药物：生物信息学和体外研究

复发性自然流产（RSA）定义为妊娠前24周内两次或两次以上连续自然流产。然而，RSA背后的详细分子机制尚不清楚。我们利用生物信息学和系统生物学的方法来分析潜在的分子机制，为RSA患者M1巨噬细胞外泌体差异表达基因（DEGs）的生物学提供新的见解，并确定治疗RSA的潜在药物。将滋养细胞HTR-8与THP-1诱导的M1巨噬细胞外泌体共培养，构建细胞模型进行转录组测序分析和数据源构建。对三组间的deg进行功能富集和途径分析。此外，通过RT-qPCR验证了关键基因的差异表达。结果从测序数据中获得172个deg。代谢和免疫相关的途径和功能是其富集的主要途径。FOCX1、GATA2、YY1、TFAP2A、MEFF2A和STAT3是RSA中M1巨噬细胞外泌体的主要转录因子（tf）。Hsa-mir-106b-5p、hsa-mir-149-3p和hsa-mir-520a-3p与RSA相关。最后，对degs -疾病和degs -药物相互作用网络进行了预测。基因本体（GO）和京都基因组百科全书（KEGG）富集分析揭示了RSA M1巨噬细胞外泌体中与母体和胎儿界面免疫耐受相关的簇和靶点。结论本研究从m1型巨噬细胞外泌体中获得的候选靶点和药物可能有助于有效治疗RSA。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.