title: Valproic acid enhances early development of bovine somatic cell nuclear transfer embryos by alleviating endoplasmic reticulum stress.
abstract: Despite the positive roles of histone deacetylase inhibitors in somatic cell nuclear transfer (SCNT), few studies have evaluated valproic acid (VPA) and its associated developmental events. Thus, the present study was conducted to elucidate the effect of VPA on the early development of bovine SCNT embryos and the underlying mechanisms of action. The histone acetylation level of SCNT embryos was successfully restored by VPA, with optimal results obtained by treatment with 3mM VPA for 24h. Importantly, the increases in blastocyst formation rate and inner cell mass and trophectoderm cell numbers were not different between the VPA and trichostatin A treatment groups, whereas cell survival was notably improved by VPA, indicating the improvement of developmental competence of SCNT embryos by VPA. Interestingly, VPA markedly reduced the transcript levels of endoplasmic reticulum (ER) stress markers, including sXBP-1 and CHOP. In contrast, the levels of GRP78/BiP, an ER stress-alleviating transcript, were significantly increased by VPA. Furthermore, VPA greatly reduced cell apoptosis in SCNT blastocysts, which was further evidenced by the increased levels of the anti-apoptotic transcript Bcl-xL and decreased level of the pro-apoptotic transcript Bax. Collectively, these results suggest that VPA enhances the developmental competence of bovine SCNT embryos by alleviating ER stress and its associated developmental damage.
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Bong-Seok
authors.initials: BS
authors.lastname: Song
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Seung-Bin
authors.initials: SB
authors.lastname: Yoon
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Bo-Woong
authors.initials: BW
authors.lastname: Sim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Jae-Jin
authors.initials: JJ
authors.lastname: Cha
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Seon-A
authors.initials: SA
authors.lastname: Choi
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Kang-Jin
authors.initials: KJ
authors.lastname: Jeong
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Ji-Su
authors.initials: JS
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Huh
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Sang-Rae
authors.initials: SR
authors.lastname: Lee
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Sang-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Sun-Uk
authors.initials: SU
authors.lastname: Kim
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
authors.forename: Kyu-Tae
authors.initials: KT
authors.lastname: Chang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle / Q000196:embryology*; D002470:Cell Survival / Q000187:drug effects; D017931:DNA Primers / Q000235:genetics; D047108:Embryonic Development / Q000187:drug effects* / Q000502:physiology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005453:Fluorescence; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006877:Hydroxamic Acids / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D053652:Nuclear Transfer Techniques / Q000662:veterinary*; D060888:Real-Time Polymerase Chain Reaction; D014635:Valproic Acid / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D017931:DNA Primers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D051028:bcl-2-Associated X Protein; C012589:trichostatin A; D014635:Valproic Acid