Targeting epigenetic nuclear reprogramming in aggregated cloned equine embryos.

The research focuses on exploring different strategies to enhance the efficiency of equine cloning by targeting nuclear reprogramming. While all assessed methods didn’t significantly improve the developmental rates, the method involving the use of chetomin allowed the creation of the first cloned foal in Australia.

About the Research

• The main aim of this research was to evaluate three different methods aimed at nuclear reprogramming to study their impact on equine somatic cell nuclear transfer (SCNT), a method involved in cloning.
• The reason for this focus is the acknowledgment that the reprogramming process frequently encounters ‘epigenetic perturbations’, which are a leading cause of low efficiency in SCNT.
• The researchers targeted the enhancement of the reprogramming process to increase the overall efficiency of the equine SCNT.

The Three Methods

• The first method involved the use of chetomin, a fungal secondary metabolite known to hinder trimethylation on histone 3 lysine 9 (H3K9 me3), to treat somatic cells. This compound is seen as a potential method to improve nuclear reprogramming.
• The second method involved the use of caffeine, a protein phosphatase inhibitor, added to the culture medium during the enucleation of oocytes and prior to the activation of reconstructed embryos with the same aims.
• The third approach involved the use of trichostatin A (TSA), a histone deacetylase inhibitor, during both embryo activation and early culture. This immunosuppressant is also seen as a candidate for improving nuclear reprogramming.

The Results

• Notably, none of these approaches significantly improved the developmental rates of in vitro aggregated cloned equine embryos. This means that the methods didn’t show any substantial benefits in the context of efficiently cloning horses.
• However, a breakthrough did occur as an outcome of the research: The first cloned equine foal born in Australia was produced with chetomin-treated somatic cells.

The Implications

• The researchers concluded that more research is needed for targeting epigenetic reprogramming to improve equine cloning efficiency, and these tried methods can serve as a starting point for future experimentation and the development of protocols.
• Emphasising on the importance of this research, the team points out how cloning, despite being costly and inefficient, has gained substantial interest in the equine industry.
• The production of the first cloned foal in Australia signifies a milestone in the field of equine cloning.