Valproic acid enhances early development of bovine somatic cell nuclear transfer embryos by alleviating endoplasmic reticulum stress
Bong-Seok Song A C , Seung-Bin Yoon A B C , Bo-Woong Sim A C , Young-Hyun Kim A B C , Jae-Jin Cha A , Seon-A Choi A , Kang-Jin Jeong A , Ji-Su Kim A , Jae-Won Huh A B , Sang-Rae Lee A , Sang-Hyun Kim A , Sun-Uk Kim A B D and Kyu-Tae Chang A B DA National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea.
B Department of Functional Genomics, University of Science and Technology, Daejeon 305-350, Republic of Korea.
C These authors contributed equally to this work.
D Corresponding authors. Emails: sunuk@kribb.re.kr; changkt@kribb.re.kr
Reproduction, Fertility and Development 26(3) 432-440 https://doi.org/10.1071/RD12336
Submitted: 12 October 2012 Accepted: 23 February 2013 Published: 19 March 2013
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 3 mM VPA for 24 h. 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.
Additional keywords: apoptosis, blastocyst, developmental competence, histone acetylation, reprogramming.
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