{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:47:01Z","timestamp":1777967221825,"version":"3.51.4"},"reference-count":49,"publisher":"Wiley","issue":"42","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2702400"],"award-info":[{"award-number":["2022YFC2702400"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2704702"],"award-info":[{"award-number":["2022YFC2704702"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2023M742932"],"award-info":[{"award-number":["2023M742932"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024T170509"],"award-info":[{"award-number":["2024T170509"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["20720240113"],"award-info":[{"award-number":["20720240113"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The mechanisms that balance a robust intrinsic antiviral defense at the maternal\u2010fetal interface with fetal development remain elusive. Here, it is delineated that ADAR1, an adenosine\u2010to\u2010inosine (A\u2010to\u2010I) editor, fine\u2010tunes intrinsic interferon (IFN)\u2010mediated integrates stress response (ISR) in the mouse placenta, thereby orchestrating embryonic development and antiviral defense. Placental\n                    <jats:italic>Adar1<\/jats:italic>\n                    deletion (\n                    <jats:italic>\n                      Adar1\n                      <jats:sup>PKO<\/jats:sup>\n                    <\/jats:italic>\n                    ) trigger spatially resolved overwhelming IFN responses, which impair the differentiation of IFN hyper\u2010responsive junctional zone (JZ) progenitors and functions of the placental JZ, ultimately causing embryonic death. Mechanistically, the\n                    <jats:italic>\n                      Adar1\n                      <jats:sup>PKO<\/jats:sup>\n                    <\/jats:italic>\n                    placental IFN hyper\u2010response is positively amplified by the accumulated immunogenic dsRNAs from the 3\u2032UTR of interferon\u2010stimulated genes (ISG\u20103\u2032UTR\u2010dsRNA). The resulting fetal death is rescued by concurrent deletion of\n                    <jats:italic>Mavs<\/jats:italic>\n                    ,\n                    <jats:italic>Ifnar1<\/jats:italic>\n                    , or\n                    <jats:italic>Pkr<\/jats:italic>\n                    , but not\n                    <jats:italic>Zbp1<\/jats:italic>\n                    or cell death effectors. Notably, blocking ISR pharmacologically preventes embryonic lethality induced by\n                    <jats:italic>\n                      Adar1\n                      <jats:sup>PKO<\/jats:sup>\n                    <\/jats:italic>\n                    JZ defects. These findings demonstrate that ADAR1 fine\u2010tunes the unique spatially resolved IFN\u2010PKR\u2010ISR signaling in the placenta by restricting ISG\u20103\u2032UTR\u2010dsRNA accumulation, highlighting a potential therapeutic strategy for treating interferonopathy\u2010associated pregnancy complications.\n                  <\/jats:p>","DOI":"10.1002\/advs.202505491","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T10:09:31Z","timestamp":1755511771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["ADAR1 as a Placental Innate Immune Rheostat Sustaining the Homeostatic Balance of Intrinsic Interferon Response at the Maternal\u2010Fetal Interface"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaogang","family":"Chen","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research Cancer Research Center Department of Obstetrics and Gynecology Women and Children's Hospital School of Medicine Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangchao","family":"Xu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research Cancer Research Center Department of Obstetrics and Gynecology Women and Children's Hospital School of Medicine Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiahao","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huiru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research Cancer Research Center Department of Obstetrics and Gynecology Women and Children's Hospital School of Medicine Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wanshan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research Cancer Research Center Department of Obstetrics and Gynecology Women and Children's Hospital School of Medicine Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenzhe","family":"Yu","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research Cancer Research Center Department of Obstetrics and Gynecology Women and Children's Hospital School of Medicine Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoqian","family":"Hu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2516-790X","authenticated-orcid":false,"given":"Bin","family":"Cao","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research Cancer Research Center Department of Obstetrics and Gynecology Women and Children's Hospital School of Medicine Xiamen University  Xiamen Fujian 361102 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat6114"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20200649"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.03.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.07.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202152450"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.11.007"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.125"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.39029"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.03.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2023.05.018"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.368"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.135"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.16.8421"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0458-6"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2414"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.10.041"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac7049"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2015.11.001"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.12.038"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature26002"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00570"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1530\/REP-21-0390"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04878-9"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.04.016"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01458-8"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00940-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04753-7"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.23101"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.76.060605.122847"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.03.025"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M310162200"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2021.07.001"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2023.09.018"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.702142"},{"key":"e_1_2_9_35_1","volume":"122","author":"Susan T.","year":"2005","journal-title":"Cell"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.60266"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.20981"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1261\/rna.079953.124"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04974-w"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exphem.2016.06.250"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04896-7"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.02.054"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aat5314"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adk1034"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1086\/379524"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-019-0237-x"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001304"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-9-352"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2563"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.202505491","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T11:29:47Z","timestamp":1763119787000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.202505491"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":49,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2025,11]]}},"alternative-id":["10.1002\/advs.202505491"],"URL":"https:\/\/doi.org\/10.1002\/advs.202505491","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,18]]},"assertion":[{"value":"2025-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-18","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e05491"}}