Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37265689", "kind": "science-record", "revision": 4, "content_hash": "sha256:52e1252666721657dd23f69e599ee7097f7791c20e2c9584e5e372834b2dff4e", "created_at": "2026-11-01T19:01:59Z", "updated_at": "2026-11-01T22:52:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Intercellular communication involving macrophages at the maternal-fetal interface may be a pivotal mechanism of URSA: a novel discovery from transcriptomic data.", "doi": "10.3389/fendo.2023.973930", "pmid": "37265689", "authors": ["Xiaoxuan Zhao", "Yuepeng Jiang", "Shiling Luo", "Yang Zhao", "Hongli Zhao"], "journal": "Frontiers in endocrinology", "year": 2023, "abstract": "Unexplained recurrent spontaneous abortion (URSA) is a severe challenge to reproductive females worldwide, and its etiology and pathogenesis have not yet been fully clarified. Abnormal intercellular communication between macrophages (Mφ) and decidual stromal cells (DSCs) or trophoblasts has been supposed to be the key to URSA. However, the exact molecular mechanisms in the crosstalk are not yet well understood. This study aimed to explore the potential molecule mechanism that may be involved in the communication between Mφ and DSC or trophoblast cells and determine their diagnostic characteristics by using the integrated research strategy of bioinformatics analysis, machine learning and experiments. First, microarrays of decidual tissue (GSE26787, GSE165004) and placenta tissue (GSE22490) in patients with URSA, as well as microarrays involving induced decidualization (GSE94644) and macrophage polarization in vitro (GSE30595) were derived from the gene expression omnibus (GEO) database. And 721 decidua-differentially expressed genes (DEGs), 613 placenta-DEGs, 510 Mφ polarization DEGs were obtained in URSA by differential expression analysis. Then, the protein-protein interaction (PPI) network was constructed, and the hub genes were identified by CytoHubba in Cytoscape software and validated by real-time PCR assay. Subsequently, immune enrichment analysis on decidua-DEGs and placenta-DEGs by ClueGO verified their regulation effects on Mφ. Besides, functional enrichment analysis was performed on Mφ polarization DEGs and the essential module genes derived from the weighted gene co-expression network analysis (WGCNA) to uncover the biological function that were related to abnormal polarization of Mφ. Furthermore, we screened out 29, 43 and 22 secreted protein-encoding genes from DSC-DEGs, placenta-DEGs and Mφ polarization DEGs, respectively. Besides, the hub secreted-protein-encoding genes were screened by CytoHubba. Moreover, we conducted functional enrichment analysis on these genes. And spearman correlation analysis between hub secreted-protein-encoding genes from donor cells and hub genes in recipient cells was performed to further understand the molecular mechanism of intercellular communication further. Moreover, signature genes with diagnostic value were screened from secreted protein-encoding genes by machine learning and validated by immunofluorescence co-localization analysis with clinical samples. Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained. In conclusion, this project provides new ideas for understanding the mechanism regulatory network of intercellular communication involving macrophages at the maternal-fetal interface of URSA. Also, it provides innovative insights for the diagnosis and treatment of URSA.", "claims": [{"id": "claim-method", "statement": "In this study, the least absolute shrinkage and selection operator (LASSO) regression analysis and support vector machine recursive feature elimination (SVM-RFE) were performed to identify secreted protein-encoding genes with diagnostic value, namely signature genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37265689", "locator": "sections[11] \"Diagnostic value of the secreted protein-encoding genes for URSA\" paragraph 2", "quote": "In this study, the least absolute shrinkage and selection operator (LASSO) regression analysis and support vector machine recursive feature elimination (SVM-RFE) were performed to identify secreted protein-encoding genes with diagnostic value, namely signature genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37265689", "locator": "sections[26] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37265689", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:37265689"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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