# Inhibition of Retinoic Acid Receptor Gamma Improves Bovine Embryo Development

## TL;DR

Blocking a specific receptor improves cow embryo development and could enhance livestock breeding.

## Contribution

Inhibiting RARγ improves bovine embryo development and metabolism, offering a new strategy for IVF optimization.

## Key findings

- LY2955303 increased blastocyst rates and embryo quality in bovine IVF.
- LY treatment enhanced glycolysis and energy metabolism in embryos and stem cells.
- Starting LY at the 16-cell stage improved glycolysis more than earlier treatment.

## Abstract

Retinoic acid receptor gamma is important in early embryo development, but its exact role is unclear. Improving embryo quality during in vitro fertilization could benefit livestock breeding. We studied how the retinoic acid receptor gamma-specific inhibitor LY2955303 affects in vitro-fertilized cow embryos. LY increased the embryo blastocyst rate compared with the control. RNA-seq revealed that LY enhanced energy production while reducing cell death and inflammation. Starting LY at the 16-cell stage improved glycolysis more than earlier treatment. It also boosted energy metabolism in bovine embryonic stem cells. This study could lead to better livestock breeding methods, improving food production and farming efficiency.

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.