Inhibition of Retinoic Acid Receptor Gamma Improves Bovine Embryo Development

Retinoic acid receptor gamma (RAR?) plays a critical but poorly understood role in early embryo development and stem cell pluripotency. Here, we investigated the effects of the RAR?-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 16-cell stage led to enhanced glycolysis in blastocysts compared with exposure from 2-cell stage. Furthermore, LY-treatment also upregulated oxidative phosphorylation in bovine embryonic stem cells (ESCs). These findings establish RAR? as an important regulator of bovine embryo development, with its inhibition offering a novel strategy to optimize IVF embryo culture systems for livestock production. Overall design: RNA-seq profiling of bovine embryos and cells, including LY2955303-treated and untreated bovine embryonic cells (bECs), and a small number of bovine embryonic stem cells (bESCs). Comparison of gene expression between treated and untreated groups to reveal the effects of LY2955303 on energy metabolism, cell death, and inflammation.