OCT4 is essential for Trophectoderm Expansion in Pigs

Abstract In pigs, OCT4 expression is maintained in the trophectoderm after the first lineage differentiation, whereas it is rapidly downregulated in mice. 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 proto-oncogene JUN, which in turn represses the anti-proliferative gene BTG2 by binding to its promoter. Disruption of this OCT4–JUN–BTG2 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.