Extended Exposure to Trichostatin-A after Activation Alters the Expression of Genes that Important for Early Development in the Nuclear Transfer Murine Embryos

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The low viability of embryos reconstructed by somatic cell nuclear transfer (SCNT) is believed to be associated with epigenetic modification errors and reduction of those errors may improve the viability of SCNT embryos. The present study shows the effect of Trichostatin-A (TSA), a strong inhibitor of histone deacetylase, on the development of murine SCNT embryos. After enucleation and nuclear injection, reconstructed murine oocytes were activated with or without TSA for 6 hr (TSA-6 hr). After activation, TSA treatment was extended to 3 hr (TSA-9 hr), 5 hr (TSA-11 hr) and 18 hr (TSA-24 hr) during the culture. As a result, the SCNT embryos in the TSA-11 hr group showed a remarkably higher blastocyst rate (21.1%) when compared to non-treated embryos (3.4%), while concentration of TSA did not significantly affect embryonic development. The expressions of histone deacetylase (HDAC1 and HDAC2) and DNA methylation (DNMT3a and DNMT3b) genes decreased in the TSA-11 hr and TSA-24 h groups, while there was an increase in the expression of histone acetyltransferase (P300 and CBP), pluripotency (OCT4 and NANOG) and embryonic growth/trophectoderm formation (FGF4)-related genes in the same groups. The expression of CDX2, a critical gene for trophectoderm formation was up-regulated only in the TSA-24 hr group. Our results show that TSA treatment during the peri- and post-activation period improves the development of reconstructed murine embryos and this observation may be explained by enhanced epigenetic modification of somatic cells caused by TSA-induced hyper-acetylation, demethylation, and up-regulation of pluripotency and embryonic growth after SCNT.

Extended Exposure to Trichostatin-A after Activation Alters the Expression of Genes that Important for Early Development in the Nuclear Transfer Murine Embryos

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