Effect of Histone Deacetylase Inhjbitors on Early Preimplantation Development in Mouse Embryo.

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Abstract
Reversible acetylation of core histone plays an important role in the regulation of gene expression and DNA replication. We examined the effect of histone deacetylase inhibitors, trichostatin A and trapoxin, on the early preimplantation development of mouse embryos. When the embryos were cultured with trapoxin and trichostatin A at the concentration at which hyperacetylation of histone is induced in the 1- and 2-cell embryos, almost all the embryos cleaved to the 2-cell stage but not to the 4-cell stage. To determine the phase in which the embryos were arrested in the second cell cycle by trapoxin, analyses of DNA synthesis and DNA stain were conducted. DNA synthesis was detected in the embryos treated with trapoxin 23 h after insemination, and chromosome condensation was not observed in the embryos arrested at the 2-cell stage 48 h after insemination. These results suggest that the embryos were arrested at the G2 phase. Immunoblotting with anti p34cdc2 antibody showed that phosphorylated forms of p34cdc2 were detected in the 2-cell arrested embryos, indicating that p34cdc2 remained in an inactive form. These results suggest that hyperacetylation of histones prevent the embryos from expressing the genes involved in the activation of p34cdc2 to inhibit p34cdc2 activation.
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