Inhibition of Retinoic Acid Receptor Gamma Improves Bovine Embryo Development

Retinoic acid receptor gamma (RARγ) plays a critical but poorly understood role in early embryo development and stem cell pluripotency. Here, we investigated the effects of the RARγ-specific inhibitor LY2955303 (LY) on in vitro-produced bovine embryos. Treatment with LY significantly increased blastocyst rates and quality, demonstrating its potential to enhance IVF outcomes in cattle. Single-embryo RNA sequencing using Smart-seq indicated that LY promotes metabolic reprogramming (upregulating glycolysis and TCA cycle activity) while suppressing apoptosis and inflammatory responses. LY treatment starting from the 16-cell stage led to enhanced glycolysis in blastocysts compared with exposure from the 2-cell stage. Furthermore, LY treatment also upregulated oxidative phosphorylation in bovine embryonic stem cells (ESCs). These findings establish RARγ as an important regulator of bovine embryo development, with its inhibition offering a novel strategy to optimize IVF embryo culture systems for livestock production.