Histone deacetylase inhibitor M344 significantly improves nuclear reprogramming, blastocyst quality, and in vitro developmental capacity of cloned pig embryos

摘要

M344 is a novel histone deacetylase inhibitor. There is no report on the effect of M344 treatment on the development of pig embryos after somatic cell nuclear transfer (SCNT). In the present study, we investigated the effect of M344 on the blastocyst formation rate in cloned embryos, acetylation level of histone H4 lysine 12 (AcH4K12), and the expression of pluripotency-related genes Oct4, NANOG, and SOX2. Our results indicated that treatment with 5 mu M M344 for 6 h improved the development of porcine embryos, in comparison with the untreated group (25.1% +/- 5.0 vs. 10.9% +/- 2.4; P 0.05). Moreover, M344-treated embryos had increased average fluorescence intensity of AcH4K12 at the pseudo-pronuclear stage (P 0.05). However, no differences exist in Oct4, NANOG, and SOX2 expression in M344-treated and untreated SCNT blastocysts. In evaluating the effect of M344 on in vivo development, 845 M344-treated embryos were transferred into 3 surrogates, 1 of whom became pregnant and developed 3 fetuses. These findings suggested that M344 elevated the level of histone acetylation, facilitated the nuclear programming, and subsequently improved the developmental competence of pig SCNT embryos.