Siriboon C.Li T.-S.CHAO-WU YUChern J.-W.Ju J.-C.2021-09-222021-09-22201819326203https://www.scopus.com/inward/record.uri?eid=2-s2.0-85053903705&doi=10.1371%2fjournal.pone.0204588&partnerID=40&md5=b2febbd216e2ad77e3103658b16fb42bhttps://scholars.lib.ntu.edu.tw/handle/123456789/583582The histone deacetylase inhibitor (HDACi) has been investigated for treating cancers and many other diseases as well as enhancing the reprogramming efficiency in cloned embryos for decades. In the present study, we investigated the effects of two novel HDAC inhibitors, i.e., HDACi-14 and -79, at the concentrations of 0, 1, 2, or 4 μM on the development of embryos cloned by the oocyte bisection cloning technique (OBCT). Blastocyst rates for the reconstructed embryos reached 60% in the 2 μM HDACi-14-treated groups, which was higher (P < 0.05) compared to the untreated group (36.9%). Similarly, HDACi-79 treatment at 2 and 4 μM also conferred higher (P < 0.05) blastocyst rates than that of the untreated group (79.4, 74.2, and 50.0%, respectively). Both HDACi-14 and -79 treatments had no beneficial effect on total cell numbers and apoptotic indices of cloned embryos (P > 0.05). Histone acetylation profile by both HDACi-14 (2 μM) and -79 (2 μM) treatments demonstrated a drastic increase (P < 0.05) mainly in two-cell stage embryos when compared to the control group. After seeding on the feeder cells, the aggregated cloned blastocysts produced by the HDACi-79 treatment showed a significant increase of primary outgrowths compared to the control group (60.0% vs. 42.9%; P < 0.05). Finally, the cloned embryo-derived ES cell lines from aggregated cloned embryos produced from the HDACi-79-treated, HDACi-14-treated and control groups were established (5, 3, and 2 lines, respectively). In conclusion, the novel histone deacetylation inhibitors improve blastocyst formation and potentially increase the derivation efficiency of ES cell lines from the cloned porcine embryos produced in vitro. Depending on the purposes, some fine-tuning may be required to maximize its beneficial effects of these newly synthesized chemicals. ? 2018 Siriboon et al.[SDGs]SDG3histone; histone deacetylase inhibitor; histone deacetylase inhibitor 14; histone deacetylase inhibitor 79; jwc 017379; jwc 022214; unclassified drug; histone; histone deacetylase inhibitor; animal cell; animal tissue; apoptosis; Article; blastocyst; cell count; cloning; concentration response; controlled study; drug mechanism; embryo; embryo aggregation; embryo development; embryonic stem cell; feeder cell; gene expression; histone acetylation; in vitro study; nonhuman; oocyte bisection cloning; pig; acetylation; animal; cell aggregation; cell line; cell nucleus transplantation; cloning; cytology; drug effect; embryo culture; embryo development; embryonic stem cell; female; karyotype; metabolism; procedures; Acetylation; Animals; Blastocyst; Cell Aggregation; Cell Line; Cloning, Organism; Embryo Culture Techniques; Embryonic Development; Embryonic Stem Cells; Female; Histone Deacetylase Inhibitors; Histones; Karyotype; Nuclear Transfer Techniques; Sus scrofajournal article10.1371/journal.pone.0204588302610202-s2.0-85053903705