{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T05:05:36Z","timestamp":1789880736942,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,16]]},"group-title":"Developmental Biology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,16]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Progesterone is essential for establishing uterine receptivity and sustaining early pregnancy. However, how the uterus acquires the competence to respond to progesterone at the appropriate time remains poorly understood. Here we show that ERBB2 governs the timing of progesterone responsiveness required for uterine receptivity. In endometrial samples from women with recurrent spontaneous abortion (RSA), ERBB2 is downregulated specifically in the stromal compartment, accompanied by a parallel reduction in stromal progesterone receptor (PGR). Uterine deletion of\n                  <jats:italic>Erbb2<\/jats:italic>\n                  in mice blunts the rise of stromal PGR at the onset of the receptive window, deferring implantation and impairing decidualization despite normal circulating progesterone and estrogen. Epithelial deletion has no such effect, placing the requirement in the stroma. High-dose progesterone fails to rescue the phenotype; advancing progesterone priming by 24 hours restores stromal PGR, HAND2,\n                  <jats:italic>Bmp2<\/jats:italic>\n                  , and on-time implantation. Collectively, the present study provides evidence that ERBB2 directs the temporal window of stromal progesterone priming by setting the threshold for PGR induction, thereby synchronizing the maternal-fetal interface and safeguarding pregnancy.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Abstract Figure<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"751518v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.14.751518","type":"posted-content","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:15:14Z","timestamp":1789618514000},"source":"Crossref","is-referenced-by-count":0,"title":["ERBB2 establishes the timing of progesterone priming required for uterine receptivity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0135-0120","authenticated-orcid":false,"given":"Bo","family":"Li","sequence":"first","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"},{"name":"Chongqing Key Laboratory of Maternal and Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Dewar","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"College of Medicine, University of Cincinnati, Cincinnati, OH 45221, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Women and Children\u2019s Hospital of Chongqing Medical University, Chongqing, 401147, China"},{"name":"Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Chongqing, 401147, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo","family":"Deng","sequence":"additional","affiliation":[{"name":"Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian 361102, China"},{"name":"State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Medicine, Xiamen University, Xiamen, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"},{"name":"Chongqing Key Laboratory of Maternal and Fetal Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9159-186X","authenticated-orcid":false,"given":"Sudhansu K.","family":"Dey","sequence":"additional","affiliation":[{"name":"Reproductive Sciences Center, Division of Developmental Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"},{"name":"College of Medicine, University of Cincinnati, Cincinnati, OH 45221, 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