Zebularine significantly improves the preimplantation development of ovine somatic cell nuclear transfer embryos
Hui Cao A C * , Jun Li
B * , Wenlong Su A C , Junjie Li A C D , Zhigang Wang A C , Shuchun Sun A C , Shujun Tian A C , Lu Li A C , Hanyang Wang A C , Jiexin Li A C , Xiaohuan Fang A C , Qiaoli Wei A C and Chuang Liu A C
+ Author Affiliations
- Author Affiliations
A College of Animal Science and Technology, Hebei Agricultural University , No. 2596 Lekai South Street, Lianchi District, Baoding 071000, PR China.
B Department of Reproductive Medicine,The First Hospital of Hebei Medical University, NO.89 Donggang Road, Yuhua District, Shijiazhuang 050031, PR China.
C Research Center of Cattle and Sheep Embryo Engineering Technique of Hebei Province, No. 2596 Lekai South Street, Lianchi District, Baoding 071000, PR China.
D Corresponding author. Email: lijunjie816@163.com
Reproduction, Fertility and Development 31(2) 357-365 https://doi.org/10.1071/RD17357
Submitted: 6 September 2017 Accepted: 14 July 2018 Published: 10 September 2018
Abstract
Aberrant DNA methylation reduces the developmental competence of mammalian somatic cell nuclear transfer (SCNT) embryos. Thus, hypomethylation-associated drugs are beneficial for improving reprogramming efficiency. Therefore, in the present study we investigated the effect of zebularine, a relatively novel DNA methyltransferase inhibitor, on the developmental potential of ovine SCNT embryos. First, reduced overall DNA methylation patterns and gene-specific DNA methylation levels at the promoter regions of pluripotency genes (octamer-binding transcription factor 4 (Oct4), SRY (sex determining region Y)-box 2 (Sox2) and Nanog) were found in zebularine-treated cumulus cells. In addition, the DNA methylation levels in SCNT embryos derived from zebularine-treated cumulus cells were significantly reduced at the 2-, 4-, 8-cell, and blastocyst stages compared with their corresponding controls (P < 0.05). The blastocyst rate was significantly improved in SCNT embryos reconstructed by the cumulus donor cells treated with 5 nM zebularine for 12 h compared with the control group (25.4±1.6 vs 11.8±1.7%, P < 0.05). Moreover, the abundance of Oct4 and Sox2 mRNA was significantly increased during the preimplantation stages after zebularine treatment (P < 0.05). In conclusion, the results indicate that, in an ovine model, zebularine decreases overall DNA methylation levels in donor cumulus cells and reconstructed embryos, downregulates the DNA methylation profile in the promoter region of pluripotency genes in donor cells and ultimately elevates the expression of pluripotency genes in the reconstructed embryos, which can lead to improved development of SCNT embryos.
Additional keywords: cumulus cell, epigenetics, reprogramming.
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