Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Beneficial effects of diazepin-quinazolin-amine derivative (BIX-01294) on preimplantation development and molecular characteristics of cloned mouse embryos

Yanfang Huang A I * , Xiaohong Jiang B C * , Miao Yu B D , Rongfu Huang E , Jianfeng Yao B F , Ming Li B , Fangfang Zheng B and Xiaoyu Yang B G H I
+ Author Affiliations
- Author Affiliations

A The First Affiliated Hospital, Fujian Medical University, Chazhong Road, 350005, Fuzhou, PR China.

B College of Preclinical Medicine, Fujian Medical University, Jiaotong Road, 350004, Fuzhou, PR China.

C Fuzhou Center for Disease Control and Prevention, Qunzhong Road, 350004, Fuzhou, PR China.

D Department of Basic Medicine, Sichuan Vocational College of Health and Rehabilitation, Huixing Road, 643000, Sichuan, PR China.

E The Second Affiliated Hospital, Fujian Medical University, Donghai Road, 362000, Quanzhou, PR China.

F Quanzhou Maternity and Child Health Care Hospital, Fengze Road, 362000, Quanzhou, PR China.

G The Affiliated Fuzhou First Hospital, Fujian Medical University, Dadao Road, 350009, Fuzhou, PR China.

H Fuzhou Maternity and Child Health Care Hospital, Liuyi Road, 350005, Fuzhou, PR China.

I Corresponding authors. Emails: yanfanghuang333@163.com; yangxiaoyu683@163.com

Reproduction, Fertility and Development 29(6) 1260-1269 https://doi.org/10.1071/RD15463
Submitted: 8 November 2015  Accepted: 4 June 2016   Published: 1 August 2016

Abstract

Somatic cell nuclear transfer is frequently associated with abnormal epigenetic modifications that may lead to the developmental failure of cloned embryos. BIX-01294 (a diazepine–quinazoline–amine derivative) is a specific inhibitor of the histone methyltransferase G9a. The aim of the present study was to investigate the effects of BIX-01294 on development, dimethylation of histone H3 at lysine 9 (H3K9), DNA methylation and the expression of imprinted genes in cloned mouse preimplantation embryos. There were no significant differences in blastocyst rates of cloned embryos treated with or without 0.1 μM BIX-01294. Relative to clone embryos treated without 0.1 μM BIX-01294, exposure of embryos to BIX-01294 decreased histone H3K9 dimethylation and DNA methylation in cloned embryos to levels that were similar to those of in vivo-fertilised embryos at the 2-cell and blastocyst stages. Cloned embryos had lower expression of octamer-binding transcription factor 4 (Oct4) and small nuclear ribonucleoprotein N (Snrpn), but higher expression of imprinted maternally expressed transcript (non-protein coding) (H19) and growth factor receptor-bound protein 10 (Grb10) compared with in vivo-fertilised counterparts. The addition of 0.1 μM BIX-01294 to the activation and culture medium resulted in lower H19 expression and higher cyclin dependent kinase inhibitor 1C (Cdkn1c) and delta-like 1 homolog (Dlk1) expression, but had no effect on the expression of Oct4, Snrpn and Grb10. The loss of methylation at the Grb10 cytosine–phosphorous–guanine (CpG) islands in cloned embryos was partially corrected by BIX-01294. These results indicate that BIX-01294 treatment of cloned embryos has beneficial effects in terms of correcting abnormal epigenetic modifications, but not on preimplantation development.

Additional keywords: DNA methylation, H3K9 me2, imprinted genes, somatic cell nuclear transfer.


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