title: Birth of Cloned Microminipigs Derived from Somatic Cell Nuclear Transfer Embryos That Have Been Transiently Treated with Valproic Acid.
abstract: In our previous study, we found that treatment of miniature pig somatic cell nuclear transfer (SCNT) embryos with 4 mM valproic acid (VPA), a histone deacetylase inhibitor, for 48 hours after activation enhanced blastocyst formation rate and octamer-binding transcription factor-3/4 (Oct-3/4) gene expression at the late blastocyst stage; however, the production of viable cloned pups failed, when those VPA-treated SCNT embryos were transferred to recipients. This failure suggests that the present VPA treatment is suboptimal. In the present study, we explored the optimal conditions for VPA to have beneficial effects on the development of SCNT embryos. When miniature pig SCNT embryos were treated with 8 mM VPA for 24 hours after activation, both the rates of blastocyst formation and blastocysts expressing the Oct-3/4 gene were significantly (p < 0.05) improved. A similar increase in blastocyst formation was also observed when microminipig-derived cells were used as SCNT donors. Five cloned piglets were obtained after the transfer of 152 microminipig SCNT embryos that had been treated with 8 mM VPA for 24 hours. The results indicated that a short duration of treatment with VPA improves the development of both miniature pig and microminipig SCNT embryos, possibly via an enhanced reprogramming mechanism.
authors.affiliation: 1 Laboratory of Animal Reproduction, Faculty of Agriculture, Kagoshima University , Kagoshima, Japan .
authors.forename: Kazuchika
authors.initials: K
authors.lastname: Miyoshi
authors.affiliation: 2 Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima, Japan .
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawaguchi
authors.affiliation: 1 Laboratory of Animal Reproduction, Faculty of Agriculture, Kagoshima University , Kagoshima, Japan .
authors.forename: Kosuke
authors.initials: K
authors.lastname: Maeda
authors.affiliation: 3 Section of Gene Expression Regulation, Center for Advanced Biomedical Science and Swine Research, Kagoshima University , Kagoshima, Japan .
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sato
authors.affiliation: 4 Department of Veterinary Histopathology, Joint Faculty of Veterinary Medicine, Kagoshima University , Kagoshima, Japan .
authors.forename: Kohei
authors.initials: K
authors.lastname: Akioka
authors.affiliation: 5 Laboratory of Theriogenology, Faculty of Veterinary Medicine, Azabu University , Kanagawa, Japan .
authors.forename: Michiko
authors.initials: M
authors.lastname: Noguchi
authors.affiliation: 2 Department of Hygiene and Health Promotion Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima, Japan .
authors.forename: Masahisa
authors.initials: M
authors.lastname: Horiuchi
authors.affiliation: 6 Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University , Kagoshima, Japan .
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
mesh_terms: D000107:Acetylation; D000818:Animals; D001755:Blastocyst / Q000166:cytology* / Q000187:drug effects; D019976:Cloning, Organism / Q000379:methods*; D004624:Embryo Transfer / Q000662:veterinary*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006657:Histones / Q000378:metabolism; D053652:Nuclear Transfer Techniques / Q000662:veterinary*; D013552:Swine; D013556:Swine, Miniature; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D006657:Histones; D014635:Valproic Acid
keywords: microminipig; reprogramming; somatic cell nuclear transfer; valproic acid