{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T01:17:05Z","timestamp":1768267025098,"version":"3.49.0"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T00:00:00Z","timestamp":1750464000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001554"],"award-info":[{"award-number":["82001554"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,6,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The differentiation of endometrial stromal cells (ESCs) into decidual stromal cells (DSCs), that is, endometrial decidualization, orchestrates the receptive environment for early embryo development, and defects in decidualization lead to unexplained recurrent spontaneous abortion (URSA). Nuclear receptor subfamily 5 group A member 1 (NR5A1) is involved in endometrial decidualization during early pregnancy, but its role is limitedly understood. Here, we elucidated the association between low expression of NR5A1 and decidualization dysregulation and URSA during early pregnancy, and then elucidated mechanisms of NR5A1 regulating decidualization. In the endometrium, the expression level of NR5A1 in secretory\u2010phase ESCs of URSA patients was lower than that of controls. During early pregnancy, the expression level of NR5A1 in DSCs from URSA patients, and that in decidua of recurrent spontaneous abortion (RSA) mice, were decreased in comparison with controls, respectively. NR5A1 knockdown impaired in\u00a0vitro decidualization of ESCs by inhibiting the IGFBP1 up\u2010regulation and F\u2010actin formation. In DSCs of early pregnancy mice, NR5A1 was maintained at a higher level from pregnant Day 4. Downknocking NR5A1 by intrauterine injection of RNAi\u2010\n                    <jats:italic>Nr5a1<\/jats:italic>\n                    lentiviruses in mice increased the embryonic resorption and impaired decidualization by down\u2010regulating the expression of\n                    <jats:italic>Dtprp<\/jats:italic>\n                    and IGFBP1. Dual\u2010luciferase reporter and ChIP\u2010qPCR assays revealed that NR5A1 bound to the\n                    <jats:italic>IGFBP1<\/jats:italic>\n                    promoter and then activated its transcription. In mice with downknocked NR5A1 in the uterus, restoring IGFBP1 expression by injecting\n                    <jats:italic>Igfbp1<\/jats:italic>\n                    \u2010overexpression lentiviruses rescued embryonic resorption. These data indicated that NR5A1 was indispensable for endometrial decidualization and that the NR5A1 reduction in secretory endometrium and early decidua may lead to URSA.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500781r","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T04:20:31Z","timestamp":1750479631000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<scp>NR5A1<\/scp>\n                    Deficiency Leads to Decidualization Dysregulation of Stromal Cells and Recurrent Spontaneous Abortion During Early Pregnancy"],"prefix":"10.1096","volume":"39","author":[{"given":"Jingcong","family":"Dai","sequence":"first","affiliation":[{"name":"Laboratory of Obstetrics and Gynecology The Second Affiliated Hospital, Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huanhuan","family":"Jiang","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyong","family":"Dong","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology Department The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Hu","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Joint International Research Lab for Reproduction and Development Ministry of Education  Chongqing China"},{"name":"Reproduction and Stem Cell Therapy Research Center of Chongqing  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2000-7894","authenticated-orcid":false,"given":"Fan","family":"He","sequence":"additional","affiliation":[{"name":"The Center for Reproductive Medicine, Obstetrics and Gynecology Department The Second Affiliated Hospital of Chongqing Medical University  Chongqing China"},{"name":"Joint International Research Lab for Reproduction and Development Ministry of Education  Chongqing China"},{"name":"Reproduction and Stem Cell Therapy Research Center of Chongqing  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tinghe","family":"Yu","sequence":"additional","affiliation":[{"name":"Laboratory of Obstetrics and Gynecology The Second Affiliated Hospital, Chongqing Medical University  Chongqing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,21]]},"reference":[{"key":"e_1_2_10_2_1","article-title":"ESHRE Guideline: Recurrent Pregnancy Loss: An Update in 2022","volume":"2023","author":"Bender Atik R.","year":"2023","journal-title":"Human Reproduction Open"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.782792"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23238"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2019.02.009"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3012"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaac006"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1061949"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12466"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12091275"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21114092"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmz146"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00019.2018"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anireprosci.2013.01.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.069435"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1780357"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2024.125503"},{"issue":"3","key":"e_1_2_10_18_1","first-page":"327","article-title":"Mutually Exclusive Interactions of Two Nuclear Orphan Receptors Determine Activity of a Cyclic Adenosine 3\u2032,5\u2032\u2010Monophosphate\u2010Responsive Sequence in the Bovine CYP17 Gene","volume":"9","author":"Bakke M.","year":"1995","journal-title":"Molecular Endocrinology"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gav045"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.018"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2200252119"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew191"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8521"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1998.4195"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1210\/er.2014-1045"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13125"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04931-x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmy035"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2004.05.002"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/31729"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deab161"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2005.11.005"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-021-04274-3"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1677\/JOE-08-0027"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2017.3867"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1051988"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2024.102095"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-3-56"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2021.111242"},{"issue":"12","key":"e_1_2_10_40_1","first-page":"2908","article-title":"The Interplay of Molecular Factors and Morphology in Human Placental Development and Implantation","volume":"12","author":"Vornic I.","year":"2024","journal-title":"Biomedicine"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.58731"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-022-00592-4"},{"issue":"16","key":"e_1_2_10_43_1","article-title":"JPT2 Affects Trophoblast Functions and Macrophage Polarization and Metabolism, and Acts as a Potential Therapeutic Target for Recurrent Spontaneous Abortion","volume":"11","author":"Chen X.","year":"2024","journal-title":"Advancement of Science"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-1673"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.074666"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06492-z"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2013.06.305"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2014-1363"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmu056"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-39008-0"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-019-0553-0"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.108.070300"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202500781R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,22]],"date-time":"2025-11-22T14:51:48Z","timestamp":1763823108000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202500781R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,21]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,6,30]]}},"alternative-id":["10.1096\/fj.202500781R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202500781r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,21]]},"assertion":[{"value":"2025-03-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70752"}}