{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:17:05Z","timestamp":1789777025904,"version":"4.0.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Key R&D Program project of the Ningxia Hui Autonomous Region","award":["2021BBF02037"],"award-info":[{"award-number":["2021BBF02037"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32172934"],"award-info":[{"award-number":["32172934"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Endometrial epithelial cell proliferation is essential for establishing endometrial receptivity during embryo implantation. In ruminants, embryonic interferon-tau (IFNT) mediates receptivity establishment by activating endometrial interferon-stimulated genes. This study investigates how IFNT-induced interferon alpha-inducible protein 6 (IFI6) regulates bovine endometrial epithelial cells (bEECs) proliferation. We identified the JAK2-STAT3 (rather than STAT1) as the primary signaling axis driving IFNT-mediated IFI6 expression. Functional experiments revealed that IFI6 knockdown markedly impaired bEECs proliferation and suppressed extracellular-regulated protein kinase (ERK1\/2) phosphorylation, while IFNT supplementation reversed these defects. Notably, pharmacological activation using RO8191 (an IFN receptor agonist) restored STAT1\/3 signaling and ERK1\/2 activation in IFI6-knockdown bEECs, normalizing their proliferation rates. Mechanistically, IFI6 functions upstream of c-Jun\/c-Fos, the major functional form of activating protein-1 (AP-1), and its knockdown disrupted ERK1\/2-dependent regulation by preventing c-Jun\/c-Fos heterodimerization and nuclear translocation. Our findings reveal that IFI6 maintains proliferative balance in bEECs by functioning as a positive feedback modulator of the IFNT-activated Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway, which subsequently triggers the ERK1\/2-c-Jun\/c-Fos signaling axis. These results provide novel insights into IFNT-mediated receptivity regulation and highlight IFI6 as a potential diagnostic marker for early pregnancy loss, as well as a therapeutic target for enhancing implantation success.<\/jats:p>","DOI":"10.1093\/biolre\/ioaf271","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T13:16:14Z","timestamp":1765458974000},"page":"598-609","source":"Crossref","is-referenced-by-count":2,"title":["Interferon-tau-induced\n                    <i>IFI6<\/i>\n                    sustains bovine endometrial epithelial cell proliferation by activating AP-1 via the JAK-STAT signaling pathway"],"prefix":"10.1093","volume":"114","author":[{"given":"Haokun","family":"Liu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]},{"name":"Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caixia","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]},{"name":"Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunmei","family":"Shang","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]},{"name":"Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]},{"name":"Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuhui","family":"Li","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]},{"name":"Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Jin","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine, Northwest A&F University , Yangling, Shaanxi ,","place":["China"]},{"name":"Key Laboratory of Animal Biotechnology, Ministry of Agriculture and Rural Affairs, Northwest A&F University , Yangling, Shaanxi 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