title: Effect of DNMT inhibitor on bovine parthenogenetic embryo development.
abstract: DNA methylation catalyzed by DNA methyltransferase (DNMT) family plays an important role during mammal preimplanted embryo development. However, the effects of RG108, a DNMT inhibitor (DNMTi), on DNMT in the development of bovine preimplanted embryos are not fully elucidated. In this study, we investigated the role of RG108 on the development, dynamics of gene-specific DNA methylation and transcription of bovine parthenogenetic preimplantation embryos. We found that Dnmt1 and Dnmt3b showed highly transcription in parthenogenetic 2-cell embryos, and then the transcription levels decreased during the following development stages, whereas Dnmt3a was always maintained at a lower transcription level during bovine parthenogenetic preimplantation embryo development. Treatment with RG108 blocked the development of bovine parthenogenetic preimplantation embryos and induced hypomethylation in the embryos. RG108 decreased the methylation level of the Nanog gene promoter region, which caused activation of the Nanog gene in 8-cell embryos and increased the transcription level. RG108 also induced the hypomethylation of the repeat elements (satellite I and α-satellite), which may cause genome instability, increasing the number of apoptotic cells in the blastocysts and also the transcription level of the apoptotic gene Bax. These results indicate that RG108, a DNMT inhibitor (DNMTi), inhibits the development of bovine parthenogenetic preimplantation embryos, suggesting that the DNMT is necessary for bovine parthenogenetic preimplanatation embryo development.
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, 130062, China; State & Local Joint Engineering Laboratory for Animal Models of Human Diseases, Academy of Translational Medicine, First Hospital, Jilin University, Changchun, Jilin, 130061, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Congli
authors.initials: C
authors.lastname: Fan
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Liuxin
authors.initials: L
authors.lastname: Shi
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, Jilin, 130062, China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State & Local Joint Engineering Laboratory for Animal Models of Human Diseases, Academy of Translational Medicine, First Hospital, Jilin University, Changchun, Jilin, 130061, China. Electronic address: sunliguang1717@vip.163.com.
authors.forename: Liguang
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Animal Science, Jilin University, Changchun, Jilin, 130062, China; State & Local Joint Engineering Laboratory for Animal Models of Human Diseases, Academy of Translational Medicine, First Hospital, Jilin University, Changchun, Jilin, 130061, China. Electronic address: ziyi@jlu.edu.cn.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019175:DNA Methylation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D066298:In Vitro Techniques; D010312:Parthenogenesis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D010797:Phthalimides / Q000494:pharmacology*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D010797:Phthalimides; C503639:RG108; D012333:RNA, Messenger; D014364:Tryptophan; D004248:DNA (Cytosine-5-)-Methyltransferases
keywords: Bovine parthenogenetic preimplantation embryos; DNA methylation; DNMT; RG108