title: Oxamflatin significantly improves nuclear reprogramming, blastocyst quality, and in vitro development of bovine SCNT embryos.
abstract: Aberrant epigenetic nuclear reprogramming results in low somatic cloning efficiency. Altering epigenetic status by applying histone deacetylase inhibitors (HDACi) enhances developmental potential of somatic cell nuclear transfer (SCNT) embryos. The present study was carried out to examine the effects of Oxamflatin, a novel HDACi, on the nuclear reprogramming and development of bovine SCNT embryos in vitro. We found that Oxamflatin modified the acetylation status on H3K9 and H3K18, increased total and inner cell mass (ICM) cell numbers and the ratio of ICM∶trophectoderm (TE) cells, reduced the rate of apoptosis in SCNT blastocysts, and significantly enhanced the development of bovine SCNT embryos in vitro. Furthermore, Oxamflatin treatment suppressed expression of the pro-apoptotic gene Bax and stimulated expression of the anti-apoptotic gene Bcl-XL and the pluripotency-related genes OCT4 and SOX2 in SCNT blastocysts. Additionally, the treatment also reduced the DNA methylation level of satellite I in SCNT blastocysts. In conclusion, Oxamflatin modifies epigenetic status and gene expression, increases blastocyst quality, and subsequently enhances the nuclear reprogramming and developmental potential of SCNT embryos.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Key Laboratory of Animal Reproductive Physiology and Embryo Technology, Ministry of Agriculture, Yangling, Shaanxi, People's Republic of China. jianminsu@163.com
authors.forename: Jianmin
authors.initials: J
authors.lastname: Su
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Li
authors.forename: Ruizhe
authors.initials: R
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wu
authors.forename: Fusheng
authors.initials: F
authors.lastname: Quan
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Zekun
authors.initials: Z
authors.lastname: Guo
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000107:Acetylation / Q000187:drug effects; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001755:Blastocyst / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D053624:Blastocyst Inner Cell Mass / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002417:Cattle; D002452:Cell Count; D065150:Cellular Reprogramming / Q000187:drug effects*; D019175:DNA Methylation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D008239:Lysine / Q000378:metabolism; D053652:Nuclear Transfer Techniques
chemical_list: D006657:Histones; D006877:Hydroxamic Acids; C100692:oxamflatin; D008239:Lysine