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Nevertheless, the functional role and downstream mechanisms of OCT4 in the TE in pigs remain entirely unexplored. By TE-specific depletion, we demonstrate that OCT4 is crucial for TE proliferation and expansion in pigs. Mechanistically, OCT4 directly binds to and activates the JUN proto-oncogene (JUN), which in turn represses the antiproliferative gene BTG anti-proliferation factor 2 (BTG2) by binding to its promoter. Disruption of this OCT4\u2013JUN\u2013BTG2 axis results in BTG2 accumulation and cell cycle arrest. Notably, knockdown of BTG2 significantly rescues the proliferation defect induced by TE-specific OCT4 depletion. This establishes a model in which OCT4 drives placental morphogenesis, offering key insights into placental evolution with direct implications for livestock reproduction.<\/jats:p>","DOI":"10.1093\/biolre\/ioag218","type":"journal-article","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:25:18Z","timestamp":1791199518000},"source":"Crossref","is-referenced-by-count":0,"title":["OCT4 is essential for trophectoderm expansion in pigs"],"prefix":"10.1093","author":[{"given":"Zicheng","family":"Qi","sequence":"first","affiliation":[{"name":"Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuang","family":"Chai","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University , Harbin ,","place":["China"]},{"name":"Tongliao Agriculture and Animal Husbandry Development Center , Tongliao ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1758-3316","authenticated-orcid":false,"given":"Jiaqiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9199-6493","authenticated-orcid":false,"given":"Zhonghua","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Animal Cellular and Genetics Engineering of Heilongjiang Province, College of Life Science, Northeast Agricultural University , Harbin ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"2026102208021590500_ref1","doi-asserted-by":"publisher","first-page":"R75","DOI":"10.1530\/REP-21-0478","article-title":"Trophectoderm formation: regulation of morphogenesis and gene expressions by RHO, ROCK, cell polarity, and HIPPO 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