title: Valproic acid treatment from the 4-cell stage improves Oct4 expression and nuclear distribution of histone H3K27me3 in mouse cloned blastocysts.
abstract: We examined effects of treatment with valproic acid (0, 0.2, 1 or 2 mM, VPA), an inhibitor of class I and IIa histone deacetylases (HDACs), of mouse somatic cell nuclear transfer (SCNT) embryos for 24 h from 48 h (4-cell stage), 24 h (2-cell stage) or immediately after oocyte activation on blastocyst formation rates and qualities of the resultant blastocysts. Blastocyst formation rates (33.4-37.0%) were not improved by VPA treatments compared with the untreated control (35.1-36.4%). However, immunofluorescence staining revealed that Oct4 expression levels, evaluated from percentages of embryos expressing Oct4 strongly and having more than 10 Oct4-positive cells, in blastocysts from SCNT embryos treated with 1 mM VPA for 24 h from the 4-cell stage (VPA-4C) were highest among all the groups and that the proportion of cells with a normal nuclear distribution of histone H3 trimethylated at lysine 27 (H3K27me3), a marker of the state of X-chromosome inactivation, significantly increased in the VPA-4C group (36.6%) compared with the control group (12.4%, P<0.05). Treatments with scriptaid and sodium butyrate, inhibitors of class I and IIa/b HDACs, for 24 h from the 4-cell stage also had beneficial effects on SCNT blastocysts. These findings indicate that treatment with 1 mM VPA from the 4-cell stage improves the Oct4 expression and nuclear distribution of H3K27me3 in mouse SCNT blastocysts and suggest that the inhibition of class I and IIa HDACs from the 4-cell stage plays an important role in these effects.
authors: Laboratory of Reproductive Biology, Graduate School of Agriculture, Kyoto University, Kyoto 606-8502, Japan.
authors: Yuuki
authors: Y
authors: Isaji
authors: Moeko
authors: M
authors: Murata
authors: Naoya
authors: N
authors: Takaguchi
authors: Toshita
authors: T
authors: Mukai
authors: Yosuke
authors: Y
authors: Tajima
authors: Hiroshi
authors: H
authors: Imai
authors: Masayasu
authors: M
authors: Yamada
mesh_terms: D000818:Animals; D001755:Blastocyst / Q000187:drug effects* / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D054885:Cumulus Cells / Q000187:drug effects / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D050814:Octamer Transcription Factor-3 / Q000235:genetics* / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D056572:Histone Deacetylase Inhibitors; D050814:Octamer Transcription Factor-3; C494174:Pou5f1 protein, mouse; D014635:Valproic Acid; D056484:Jumonji Domain-Containing Histone Demethylases; C523761:Kdm6b protein, mouse