Effects of Histone Deacetylase Inhibitors on the Early Development of Bovine Androgenetic Embryos

Abstract

Histone acetylation is one of the most important posttranslational modifications that contribute to transcriptional initiation and chromatin remodeling. In our previous study, we enhanced sperm chromatin remodeling within the bovine sperm injection-derived androgenentic (SpI-AG) embryos by sperm pretreatment, and thereby improved their early developmental competence. In this study, we found that blastocyst development of SpI-AG embryos could be elevated by the histone deacetylase inhibitor (HDACi). First, we optimized the efficacy of two histone deacetylase inhibitors [trichostatin A (TSA) and Scriptaid (SCR)] in a dose (0, 5, 10, 20, 50, and 100 nM for TSA; 0, 50, 100, 200, 300, and 500 nM for SCR, respectively) and time-dependent (0, 10, 15, 20, and 25 h) manner on the developmental capacity of these embryos. Furthermore, we quantitatively assessed the alterations in histone H3 and H4 overall acetylation levels and blastocyst quality of SpI-AG embryos by immunofluorescence staining. We found a significantly improved morula and blastocyst development rate of SpI-AG embryos at a mild dose of TSA (20 nM) or SCR (200 nM) for 15 h after embryo activation. Furthermore, both HDACi noticeably increased the levels of acetylated histone H3 and H4 in SpI-AG blastocyst embryos, whereas, SCR treatment improved the quality of blastocysts when compared with control group. In conclusion, HDACi is beneficial for early development of bovine SpI-AG embryos and can be used to improve the efficiency of its in vitro production.