{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T15:09:48Z","timestamp":1783523388540,"version":"3.55.0"},"reference-count":58,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,3,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The human decidua establishes immune tolerance at the maternal\u2013fetal interface and is essential for successful embryo implantation and development. Here, we conducted a spatial transcriptomic analysis of human decidua from early pregnancies in both healthy donors and patients with recurrent pregnancy loss (RPL). Our analysis revealed two distinct spatial domains, named implantation zone (IZ) and glandular-secretory zone (GZ), corresponding to the layers of decidua compacta and spongiosa, respectively. The decidual natural killer cell subset (dNK1) and the decidual macrophage subset (dM2), both associated with growth promotion and immune regulation, were predominantly localized in the healthy IZ but were significantly reduced in RPL patients. In contrast, cytotoxic CD8+ T cells, sparsely distributed in the healthy decidual IZ and GZ domains, were elevated in both domains under RPL conditions. Spatial cell\u2013cell interaction analysis indicated a broad exhibition but a marked downregulation of immunoregulatory interactions in the IZ of RPL patients. Through integrated single-cell chromatin accessibility and transcription factor occupancy analyses, we identified FOSL2 as a pivotal regulator orchestrating the spatial transformation of dNK1 cells. Decreased FOSL2 expression correlated with compromised IL-15-induced dNK1 cell transformation and diminished immunoregulatory capabilities. Our findings delineate the intricate spatial and regulatory architecture of immune tolerance within the human decidua, providing new insights into immune tolerance dysregulation in RPL.<\/jats:p>","DOI":"10.1093\/gpbjnl\/qzaf080","type":"journal-article","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:56:29Z","timestamp":1759312589000},"source":"Crossref","is-referenced-by-count":3,"title":["Spatial Transcriptomics of Human Decidua Identifies Molecular Signatures in Recurrent Pregnancy Loss"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8604-1975","authenticated-orcid":false,"given":"Qing","family":"Sha","sequence":"first","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3272-7119","authenticated-orcid":false,"given":"Qiaoni","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8485-1432","authenticated-orcid":false,"given":"Kaixing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"Institute of Artificial Intelligence, Hefei Comprehensive National Science Center , Hefei 230088,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0621-3435","authenticated-orcid":false,"given":"Junyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7866-5497","authenticated-orcid":false,"given":"Feiyang","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Stem Cell and Reproductive Biology, Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1415-185X","authenticated-orcid":false,"given":"Chen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"Institute of Artificial Intelligence, Hefei Comprehensive National Science Center , Hefei 230088,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1474-2809","authenticated-orcid":false,"given":"Yuanzhe","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"Institute of Artificial Intelligence, Hefei Comprehensive National Science Center , Hefei 230088,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9780-7232","authenticated-orcid":false,"given":"Meifang","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6028-7578","authenticated-orcid":false,"given":"Yanbing","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9754-1492","authenticated-orcid":false,"given":"Ke","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0147-651X","authenticated-orcid":false,"given":"Kun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8272-3728","authenticated-orcid":false,"given":"Zongcheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"Department of Stomatology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3780-5190","authenticated-orcid":false,"given":"Shouzhen","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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Science and Technology of China , Hefei 230001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7889-1697","authenticated-orcid":false,"given":"Jianping","family":"Weng","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Clinical Research Hospital of Chinese Academy of Sciences (Hefei), University of Science and Technology of China , Hefei 230001,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5555-8437","authenticated-orcid":false,"given":"Kun","family":"Qu","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"Institute of Artificial Intelligence, Hefei Comprehensive National Science Center , Hefei 230088,","place":["China"]},{"name":"School of Biomedical Engineering, Suzhou Institute for Advanced Research, University of Science and Technology of China , Suzhou 215123,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3912-0793","authenticated-orcid":false,"given":"Chuang","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Oncology, The First Affiliated Hospital of USTC, State Kye Laboratory of Eye Health, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"Department of Rheumatology and Immunology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei 230021,","place":["China"]},{"name":"School of Pharmacy, Bengbu Medical University , Bengbu 233030,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,10,1]]},"reference":[{"key":"2026060719312918200_qzaf080-B1","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1387\/ijdb.082764gb","article-title":"The influence of the intrauterine environment on human placental development","volume":"54","author":"Burton","year":"2010","journal-title":"Int J Dev Biol"},{"key":"2026060719312918200_qzaf080-B2","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":"2026060719312918200_qzaf080-B3","doi-asserted-by":"crossref","first-page":"7970","DOI":"10.1038\/s41598-020-64512-4","article-title":"Machine learning (ML) based-method applied in 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