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ISSN 2052-1472 (online)

Reproduction Abstracts (2014) 1 P072 | DOI: 10.1530/repabs.1.P072

Treatment of histone deacetylase inhibitor increases in vitro developmental competence of bovine cloned embryos through suppression of endoplasmic reticulum stress

Sun-Uk Kim, Pil-Soo Jeong, Hae-Jun Yang, Seong-Eun Mun, Seon-A Choi, Seung-Bin Yoon, Young-Ho Park, Bong-Seok Song, Bo-Woong Sim, Ji-Su Kim & Kyu-Tae Chang

KRIBB, Chungcheongbuk-do, Republic of Korea

Although the beneficial roles of HDAC inhibitors (HDACis) in somatic cell nuclear transfer (SCNT) were known, few studies have conducted concerning the role of valproic acid (VPA) as an efficient HDACi for SCNT and its associated developmental event(s). Thus, the present study was carried out to determine the effect of VPA on developmental competence of bovine SCNT embryos and the underlying mechanism(s). We showed that the VPA treatment restored the histone acetylation level of SCNT embryos similar to IVF embryos, with optimal results obtained by treatment with 3 mM VPA for 24 h. Importantly, although blastocyst formation rate and ICM and TE cell numbers were not different between the VPA and trichostatin A (TSA) treatment groups, cell survival was significantly 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 reduces apoptotic cells in SCNT blastocysts, which was further evidenced by the increased levels of 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.