Comparison between the effects of valproic acid and thricostatin on the in vitro development, blastocyst quality and full-term development of mouse somatic cell nuclear transfer embryos

Reprogramming of differentiated nuclei into a totipotent embryonic state following somatic cell nuclear transfer(SCNT) is not efficient. Previous studies in the hybrid B6D2F1 mouse strain revealed that a transient treatment ofthe SCNT embryos with the histone deacetylase inhibitor (HDACi) trichostatin A (TSA) significantly enhance thepotential of the cloned embryos to develop in vitro and to term. Here, we compare two different SCNT protocolswith TSA and explore, for the first time, the effect of another HDACi, valproic acid (VPA), on the in vitrodevelopment, blastocyst quality, and full-term development of mouse B6CBAF1 cloned embryos. Rates ofblastocyst development in SCNT embryos treated with either 5 nM TSA during and after activation (31.8%) orwith 100nM TSA or 2mM VPA before and during activation (34.5 and 38.3%, respectively) were clearly superiorto those of nontreated SCNT embryos (22.9–25.1%). These increased in vitro development rates of the HDACitreatedembryos were correlated with an increased level of histone H3 lysine 14 acetylation and an improvedblastocyst quality, as judged by the increased number of total and ICM cells in comparison to the nontreatedembryos (30–35% increase). Treatment of SCNT embryos with TSA or VPA also allowed the obtention of viablecloned mice, whereas none could be produced from untreated SCNT embryos. In conclusion, we have demonstratedfor the first time that VPA can improve the in vitro and full-term development of B6CBAF1 SCNTembryos, at a similar level as TSA. Our findings may open new opportunities to improve cloning efficiencies inother mouse strains or species.