Inhibition of Retinoic Acid Receptor Gamma Improves Bovine Embryo Development

  • Vet Sci. 2025 Sep 24;12(10):924. doi: 10.3390/vetsci12100924.
Xiangyan Wang  1  2 ,  Wenjing Wan  1 ,  Yue Su  1 ,  Shengcan Xie  1 ,  Fenfen Jiang  1 ,  Zhen Yang  1 ,  Shuangyi Xiehe  1 ,  Wei Ma  1 ,  Linxiu Yue  1 ,  Ningxiao Li  1 ,  Ahui Wang  1 ,  Jintong Guo  1 ,  Xiaoting Li  1 ,  Xinfeng Liu  2 ,  Young Tang  1  2
Affiliations
  • 1. Key Laboratory of Livestock Biology, Shanxi Centre of Stem Cells Engineering & Technology, College of Veterinary Medicine, Northwest A&F University, Yangling 712100, China.
  • 2. Key Laboratory of Ministry of Education for Conservation and Utilization of Special Biological Resources in the Western, Ningxia University, Yinchuan 750021, China.
PMID: 41150070 DOI: 10.3390/vetsci12100924
Abstract

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.

Keywords
RARγ; bovine embryo; metabolic reprogramming.
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