Trichostatin A improves histone acetylation in bovine somatic cell nuclear transfer early embryos

Growing evidence suggests that epigenetic misregulation may underlie faulty reprogramming following somatic cell nuclear transfer (SCNT) cloning in mammals. It has therefore been of interest to target chromatin modifications as a means of improving the efficiency of SCNT production. Recent studies have shown that use of a specific histone deacetylase inhibitor, trichostatin A (TSA), can significantly improve the efficiency of full-term development of mice produced through cloning. The objective of the current study was to investigate what effect treatment of activated bovine SCNT embryos with TSA had on the developmental potential of such embryos, based on several parameters. Specifically, we determined that the preimplantation developmental quality of TSA-treated SCNT embryos was similar to fertilized counterparts. Semi-quantification of acetylation of histone 4 at lysine 5 (AcH4K5) in bovine SCNT 8-cell embryos revealed that TSA treatment resulted in embryos with AcH4K5 levels similar to those in IVF embryos and significantly greater than in untreated SCNT 8-cell embryos. Finally, quantitative RT-PCR analysis of 8 developmentally important genes in single blastocysts showed a similar expression profile for 5 genes among all treatment groups, while expression of 3 genes was greater in TSA-treated SCNT embryos than in fertilized blastocysts.