{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:45:23Z","timestamp":1792046723788,"version":"4.4.0"},"reference-count":42,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This study aims to explore the potential mechanisms contributing to recurrent pregnancy loss (RPL) and identify potential biomarkers. We analyzed endometrial samples from 39 RPL and 22 healthy controls using proteomics, identifying differentially expressed proteins (DEPs) with DEqMS and quantifying immune cell infiltration with CIBERSORT. We also examined a decidual scRNA-seq dataset (CRA002181) to identify macrophage marker genes, performed WGCNA to correlate macrophage infiltration with protein expression, and conducted functional enrichment analysis. Immunofluorescence staining was conducted to quantify the proportions of CD3+, CD8a+, CD68+, and CD206+ cells, and Western blot analysis was performed to determine MMP9 expression in endometrial tissues from RPL and controls. M2 macrophages and CD8+ T cells were enriched in the endometrium of RPL. Proteomic analysis of endometrial tissues from RPL identified 310 DEPs associated with immune response, cell adhesion, and secretory granule processes. From the scRNA-seq dataset, 295 macrophage marker genes were identified. WGCNA revealed that the brown module exhibited the highest correlation with macrophage infiltration. MMP9 emerged as the sole intersecting candidate, showing marked downregulation in RPL. Mendelian randomization analysis showed that genetically predicted higher circulating MMP9 levels decrease RPL risk (OR 0.75, 95% CI 0.57\u20130.98; P =\u20090.036). Additionally, RPL patients showed significantly higher proportions of CD3+CD8a+ cells (P &amp;lt; 0.05) and CD68+CD206+ cells (P = 0.265), and decreased MMP9 protein expression (P &amp;lt; 0.05), compared with controls. In conclusion, this study indicates that an imbalance in endometrial M2 macrophage and CD8+ T cell immune infiltration is associated with RPL. MMP9 may represent a potential predictive biomarker for RPL.<\/jats:p>","DOI":"10.1093\/biolre\/ioag146","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T16:05:20Z","timestamp":1784045120000},"page":"1226-1238","source":"Crossref","is-referenced-by-count":0,"title":["Multi-omics analyses link dysregulated immune hemostasis to decreased endometrial MMP protein in recurrent pregnancy loss"],"prefix":"10.1093","volume":"115","author":[{"given":"Ruifang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Lanzhou University Second Hospital , Lanzhou ,","place":["China"]},{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology , Luoyang ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Lanzhou University Second Hospital , Lanzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangxiang","family":"Mu","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Lanzhou University Second Hospital , Lanzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Lanzhou University Second Hospital , Lanzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7895-374X","authenticated-orcid":false,"given":"Fang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Lanzhou University Second Hospital , Lanzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,14]]},"reference":[{"key":"2026101502075079600_ref1","volume-title":"Recurrent Pregancy Loss: Guideline of European Society of Human Reproduction and Embryology","author":"ESHRE Recurrent Pregnancy Loss Guideline Development Group","year":"2022"},{"key":"2026101502075079600_ref2","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.1016\/S0140-6736(21)00682-6","article-title":"Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss","volume":"397","author":"Quenby","year":"2021","journal-title":"Lancet"},{"key":"2026101502075079600_ref3","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41572-020-00228-z","article-title":"Recurrent pregnancy loss","volume":"6","author":"Dimitriadis","year":"2020","journal-title":"Nat Rev Dis Primers"},{"key":"2026101502075079600_ref4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1111\/j.1600-0897.2004.00156.x","article-title":"Macrophages and apoptotic cell clearance during pregnancy","volume":"51","author":"Abrahams","year":"2004","journal-title":"Am J Reprod Immunol"},{"key":"2026101502075079600_ref5","doi-asserted-by":"crossref","first-page":"453","DOI":"10.37349\/ei.2023.00113","article-title":"Research progress of immune balance and genetic polymorphism in unexplained recurrent abortion","volume":"3","author":"Kang","year":"2023","journal-title":"Exploration of Immunology"},{"key":"2026101502075079600_ref6","doi-asserted-by":"crossref","first-page":"792","DOI":"10.3389\/fimmu.2019.00792","article-title":"Macrophage Polarization in Physiological and Pathological Pregnancy","volume":"10","author":"Yao","year":"2019","journal-title":"Front Immunol"},{"key":"2026101502075079600_ref7","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1620\/tjem.2024.J069","article-title":"A Review on the Potential Therapeutic Application of Macrophage Polarization in Recurrent Spontaneous Abortion; 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