{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T08:17:19Z","timestamp":1772785039938,"version":"3.50.1"},"reference-count":31,"publisher":"CSIRO Publishing","issue":"3","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":4452,"URL":"https:\/\/doi.org\/10.1071\/journalslicense"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,3,12]]},"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.1071\/rd12336","type":"journal-article","created":{"date-parts":[[2013,3,18]],"date-time":"2013-03-18T20:02:19Z","timestamp":1363636939000},"page":"432-440","source":"Crossref","is-referenced-by-count":24,"title":["Valproic acid enhances early development of bovine somatic cell nuclear transfer embryos by alleviating endoplasmic reticulum stress"],"prefix":"10.1071","volume":"26","author":[{"given":"Bong-Seok","family":"Song","sequence":"first","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"CThese authors contributed equally to this work."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seung-Bin","family":"Yoon","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"BDepartment of Functional Genomics, University of Science and Technology, Daejeon 305-350, Republic of Korea."},{"name":"CThese authors contributed equally to this work."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo-Woong","family":"Sim","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"CThese authors contributed equally to this work."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"BDepartment of Functional Genomics, University of Science and Technology, Daejeon 305-350, Republic of Korea."},{"name":"CThese authors contributed equally to this work."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Jin","family":"Cha","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seon-A","family":"Choi","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kang-Jin","family":"Jeong","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Su","family":"Kim","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jae-Won","family":"Huh","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"BDepartment of Functional Genomics, University of Science and Technology, Daejeon 305-350, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Rae","family":"Lee","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun-Uk","family":"Kim","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"BDepartment of Functional Genomics, University of Science and Technology, Daejeon 305-350, Republic of Korea."},{"name":"DCorresponding authors. Emails:"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu-Tae","family":"Chang","sequence":"additional","affiliation":[{"name":"ANational Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungcheongbuk-do 363-883, Republic of Korea."},{"name":"BDepartment of Functional Genomics, University of Science and Technology, Daejeon 305-350, Republic of Korea."},{"name":"DCorresponding authors. Emails:"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"67","published-online":{"date-parts":[[2013,3,19]]},"reference":[{"key":"2025102819420078500_R1","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/S0028-3908(00)00029-0","article-title":"Increased expression of endoplasmic reticulum stress proteins following chronic valproate treatment of rat C6 glioma cells.","volume":"39","author":"Bown","year":"2000","journal-title":"Neuropharmacology"},{"key":"2025102819420078500_R2","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/S0006-3223(00)00878-7","article-title":"Chronic valproate treatment increases expression of endoplasmic reticulum stress proteins in the rat cerebral cortex and hippocampus.","volume":"48","author":"Chen","year":"2000","journal-title":"Biol. Psychiatry"},{"key":"2025102819420078500_R3","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1089\/CELL.2009.0108","article-title":"Comparison between the effects of valproic acid and trichostatin A on the in vitro development, blastocyst quality and full-term development of mouse somatic cell nuclear transfer embryos.","volume":"12","author":"Costa-Borges","year":"2010","journal-title":"Cell Reprogram."},{"key":"2025102819420078500_R4","doi-asserted-by":"publisher","first-page":"6969","DOI":"10.1093\/EMBOJ\/20.24.6969","article-title":"Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells.","volume":"20","author":"Gottlicher","year":"2001","journal-title":"EMBO J."},{"key":"2025102819420078500_R5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1095\/BIOLREPROD66.1.6","article-title":"Frequency and occurrence of late-gestation losses from cattle cloned embryos.","volume":"66","author":"Heyman","year":"2002","journal-title":"Biol. Reprod."},{"key":"2025102819420078500_R6","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/S0093-691X(98)00227-1","article-title":"Developmental kinetics of the first cell cycles of bovine in vitro-produced embryos in relation to their in vitro viability and sex.","volume":"50","author":"Holm","year":"1998","journal-title":"Theriogenology"},{"key":"2025102819420078500_R7","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1038\/NBT1418","article-title":"Induction of pluripotent stem cells by defined factors is greatly improved by small-molecule compounds.","volume":"26","author":"Huangfu","year":"2008","journal-title":"Nat. Biotechnol."},{"key":"2025102819420078500_R8","doi-asserted-by":"publisher","first-page":"12 889","DOI":"10.1073\/PNAS.192433399","article-title":"Abnormal gene expression in cloned mice derived from embryonic stem cell and cumulus cell nuclei.","volume":"99","author":"Humpherys","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025102819420078500_R9","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.1038\/NBT.1678","article-title":"Epigenetic modifications as therapeutic targets.","volume":"28","author":"Kelly","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"2025102819420078500_R10","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1242\/JCS.01562","article-title":"Valproate protects cells from ER stress-induced lipid accumulation and apoptosis by inhibiting glycogen synthase kinase-3.","volume":"118","author":"Kim","year":"2005","journal-title":"J. Cell Sci."},{"key":"2025102819420078500_R11","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1007\/S11626-011-9394-7","article-title":"Comparison of potency between histone deacetylase inhibitors trichostatin A and valproic acid on enhancing in vitro development of porcine somatic cell nuclear transfer embryos.","volume":"47","author":"Kim","year":"2011","journal-title":"In Vitro Cell. Dev. Biol. Anim."},{"key":"2025102819420078500_R12","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1111\/J.1439-0531.2011.01969.X","article-title":"Tauroursodeoxycholic acid enhances the pre-implantation embryo development by reducing apoptosis in pigs.","volume":"47","author":"Kim","year":"2012","journal-title":"Reprod. Domest. Anim."},{"key":"2025102819420078500_R13","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1095\/BIOLREPROD67.2.487","article-title":"Aberrant allocations of inner cell mass and trophectoderm cells in bovine nuclear transfer blastocysts.","volume":"67","author":"Koo","year":"2002","journal-title":"Biol. Reprod."},{"key":"2025102819420078500_R14","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1262\/JRD.10-012A","article-title":"Trichostatin A promotes the development of bovine somatic cell nuclear transfer embryos.","volume":"57","author":"Lee","year":"2011","journal-title":"J. Reprod. Dev."},{"key":"2025102819420078500_R15","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/SJ.CDD.4401778","article-title":"ER stress and neurodegenerative diseases.","volume":"13","author":"Lindholm","year":"2006","journal-title":"Cell Death Differ."},{"key":"2025102819420078500_R16","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1089\/CELL.2009.0032","article-title":"Valproic acid enhances in vitro development and Oct-3\/4 expression of miniature pig somatic cell nuclear transfer embryos.","volume":"12","author":"Miyoshi","year":"2010","journal-title":"Cell Reprogram."},{"key":"2025102819420078500_R17","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1095\/BIOLREPROD.110.085282","article-title":"Inhibition of class IIb histone deacetylase significantly improves cloning efficiency in mice.","volume":"83","author":"Ono","year":"2010","journal-title":"Biol. Reprod."},{"key":"2025102819420078500_R18","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/0093-691X(86)90143-3","article-title":"Bovine in vitro fertilization with frozen\u2013thawed semen.","volume":"25","author":"Parrish","year":"1986","journal-title":"Theriogenology"},{"key":"2025102819420078500_R19","first-page":"303","article-title":"Factors influencing the commercialisation of cloning in the pork industry.","volume":"62","author":"Pratt","year":"2006","journal-title":"Soc. Reprod. Fertil. Suppl."},{"key":"2025102819420078500_R20","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1071\/RD10194","article-title":"Inactivated Sendai virus-mediated fusion improves early development of cloned bovine embryos by avoiding endoplasmic reticulum-stress-associated apoptosis.","volume":"23","author":"Song","year":"2011","journal-title":"Reprod. Fertil. Dev."},{"key":"2025102819420078500_R21","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1530\/JRF.0.1040251","article-title":"Ratio of inner cell mass and trophoblastic cells in demi- and intact pig embryos.","volume":"104","author":"Tao","year":"1995","journal-title":"J. Reprod. Fertil."},{"key":"2025102819420078500_R22","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1071\/RD06089","article-title":"Somatic cell nuclear transfer in pigs: recent achievements and future possibilities.","volume":"19","author":"Vajta","year":"2007","journal-title":"Reprod. Fertil. Dev."},{"key":"2025102819420078500_R23","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1007\/S12192-011-0306-2","article-title":"A quantitative method for detection of spliced X-box binding protein-1 (XBP1) mRNA as a measure of endoplasmic reticulum (ER) stress.","volume":"17","author":"van Schadewijk","year":"2012","journal-title":"Cell Stress Chaperones"},{"key":"2025102819420078500_R24","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1530\/REP-06-0109","article-title":"Temporal detection of caspase-3 and -7 in bovine in vitro-produced embryos of different developmental capacity.","volume":"133","author":"Vandaele","year":"2007","journal-title":"Reproduction"},{"key":"2025102819420078500_R25","doi-asserted-by":"publisher","first-page":"6048","DOI":"10.1074\/JBC.M511340200","article-title":"Inheritable histone H4 acetylation of somatic chromatins in cloned embryos.","volume":"281","author":"Wee","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025102819420078500_R26","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1089\/CELL.2010.0087","article-title":"Scriptaid corrects gene expression of a few aberrantly reprogrammed transcripts in nuclear transfer pig blastocyst stage embryos.","volume":"13","author":"Whitworth","year":"2011","journal-title":"Cell Reprogram."},{"key":"2025102819420078500_R27","doi-asserted-by":"publisher","first-page":"2656","DOI":"10.1172\/JCI26373","article-title":"Endoplasmic reticulum stress: cell life and death decisions.","volume":"115","author":"Xu","year":"2005","journal-title":"J. Clin. Invest."},{"key":"2025102819420078500_R28","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1089\/cell.2011.0084","article-title":"Valproic acid improves the in vitro development competence of bovine somatic cell nuclear transfer embryos.","volume":"14","author":"Xu","year":"2012","journal-title":"Cell Reprogram."},{"key":"2025102819420078500_R29","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/NG1973","article-title":"Nuclear reprogramming of cloned embryos and its implications for therapeutic cloning.","volume":"39","author":"Yang","year":"2007","journal-title":"Nat. Genet."},{"key":"2025102819420078500_R30","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1016\/J.NEULET.2011.09.003","article-title":"Valproate protects the retina from endoplasmic reticulum stress-induced apoptosis after ischemia-reperfusion injury.","volume":"504","author":"Zhang","year":"2011","journal-title":"Neurosci. Lett."},{"key":"2025102819420078500_R31","doi-asserted-by":"publisher","first-page":"e40433","DOI":"10.1371\/JOURNAL.PONE.0040433","article-title":"Inhibition of endoplasmic reticulum stress improves mouse embryo development.","volume":"7","author":"Zhang","year":"2012","journal-title":"PLoS ONE"}],"container-title":["Reproduction, Fertility and Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/26\/3\/432\/310819\/rd12336.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/connectsci.au\/rd\/article-pdf\/26\/3\/432\/310819\/rd12336.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T23:42:07Z","timestamp":1761694927000},"score":1,"resource":{"primary":{"URL":"https:\/\/connectsci.au\/rd\/article\/26\/3\/432\/50013\/Valproic-acid-enhances-early-development-of-bovine"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,3,19]]},"references-count":31,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2014,3,12]]}},"URL":"https:\/\/doi.org\/10.1071\/rd12336","relation":{},"ISSN":["1031-3613","1448-5990"],"issn-type":[{"value":"1031-3613","type":"print"},{"value":"1448-5990","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,3,19]]}}}