Effect of histone deacetylase inhibitors on preimplantation development and zygotic gene activation of cloned bovine embryos

Abstract

This study was carried out to examine the effect of histone deacetylase inhibitors (HDACis) on the preimplantation development and zygotic gene activation (ZGA). Trichostatin A (TSA) and scriptaid (SCR) were the HDACis used in this research. TSA is a potent histone deacetylase inhibitors; however, the chemical was reported to be toxic to the development of embryos, and scriptaid, a novel HDACi, which was reported to be less toxic to embryos, both HDACis have been revealed in various studies to be able to increase the developmental rate of embryo during preimplantation development. In the experiment of TSA treatment, the blastocyst formation rate was highest in 2-step group (30.1%) which was significantly higher than 1-step group (20.0%) and control group (9.1%). In the experiment of Scriptaid treatment, the second treatment there were significant differences in the blastocyst rates of each group – 15.7%, 33.3%, 50.0% for control, 1-step and 2-step group, respectively. The newly optimized 2-step treatment, in which the time point was changed to 52h-62h, resulted in a noticeable improvement of blastocyst quality with the cell number per blastocyst being 45.8 ± 5.9 (control), 61 ± 17.6 (1-step), 92.3 ± 8.9 (2-step). In addition, global histone acetylation and nascent mRNA was further enhanced with the treated embryos showed the signal intensity to be nearly 2 times more than that of the non-treated embryos. Keywords: trichostatin A (TSA), scriptaid (SCR), cloned bovine embryo, preimplantation development, zygotic gene activation