TBX3 is Essential for Zygotic Genome Activation and Embryonic Development in Pigs

Microsc Microanal. 2025 Jan 13:ozae123. doi: 10.1093/mam/ozae123. Online ahead of print.

Abstract

The pluripotency-related T-box family transcription factor TBX3 maintains mESC self-renewal and plays a key role in the development of several tissues, including the heart, mammary glands, limbs, and lungs. However, the role of TBX3 during porcine preimplantation embryo development remains unclear. In our research, TBX3 was knocked down by injecting dsRNA to explore the function of TBX3. TBX3 expression gradually increases during early embryonic development. TBX3 knockdown resulted in decreased in the rate of four-cell and blastocyst. Depletion of TBX3 decreased the level of H3K9Ac/H3K27Ac and decreased ZGA gene expression at the four-cell stage. Furthermore, TBX3 knockdown led to a decrease in ZSACN4 protein level, DNMT1 and intracellular 5mc levels were increased, and then induced telomeres shorten and DNA damaged. Additionally, TBX3 knockdown significantly decreased histone acetylation and pluripotency genes NANOG/OCT4 expression in blastocysts. TBX3 knockdown induced apoptosis in blastocysts. Taken together, TBX3 regulate histone acetylation and play important roles in zygotic genome activation and early embryonic development in pigs.

Keywords: TBX3; ZGA; embryo development; histone acetylation; pig.