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题名: Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish
作者: Xia, Hui1, 2; Zhong, Chengrong1; Wu, Xingxing1, 2; Chen, Ji1; Tao, Binbin1, 2; Xia, Xiaoqin1; Shi, Mijuan1; Zhu, Zuoyan1; Trudeau, Vance L.3; Hu, Wei1
关键词: mettl3 ; N-6-methyladenosine ; gamete maturation ; fertility ; zebrafish
刊名: GENETICS
发表日期: 2018-02-01
DOI: 10.1534/genetics.117.300574
卷: 208, 期:2, 页:729-743
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ; Life Sciences & Biomedicine
类目[WOS]: Genetics & Heredity
研究领域[WOS]: Genetics & Heredity
英文摘要: N-6-methyladenosine (m(6)A), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous studies have implicated m(6)A modification in multiple biological processes, but the in vivo function of m(6)A has been difficult to study, because mettl3 mutants are embryonic lethal in both mammals and plants. In this study, we have used transcription activator-like effector nucleases and generated viable zygotic mettl3 mutant, Zmettl3(m/m), in zebrafish. We find that the oocytes in Zmettl3(m/m) adult females are stalled in early development and the ratio of full-grown stage (FG) follicles is significantly lower than that of wild type. Human chorionic gonadotropin-induced ovarian germinal vesicle breakdown in vitro and the numbers of eggs ovulated in vivo are both decreased as well, while the defects of oocyte maturation can be rescued by sex hormone in vitro and in vivo. In Zmettl3(m/m) adult males, we find defects in sperm maturation and sperm motility is significantly reduced. Further study shows that 11-ketotestosterone (11-KT) and 17-estradiol (E2) levels are significantly decreased in Zmettl3(m/m), and defective gamete maturation is accompanied by decreased overall m(6)A modification levels and disrupted expression of genes critical for sex hormone synthesis and gonadotropin signaling in Zmettl3(m/m). Thus, our study provides the first in vivo evidence that loss of Mettl3 leads to failed gamete maturation and significantly reduced fertility in zebrafish. Mettl3 and m(6)A modifications are essential for optimal reproduction in vertebrates.
关键词[WOS]: MESSENGER-RNA METHYLATION ; GENE-EXPRESSION REGULATION ; MEDAKA ORYZIAS-LATIPES ; EMBRYONIC STEM-CELLS ; OOCYTE MATURATION ; SEX DETERMINATION ; NUCLEAR-RNA ; STEREOLOGICAL EVALUATION ; BRACHYDANIO-RERIO ; DANIO-RERIO
语种: 英语
项目资助者: National Natural Science Foundation(31325026 ; Chinese Academy of Sciences(XDA08010106 ; University of Ottawa International Research Acceleration Program ; 31721005 ; 2016FBZ03) ; 31461163006)
WOS记录号: WOS:000423563400020
ISSN号: 0016-6731
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.ihb.ac.cn/handle/342005/50646
Appears in Collections:鱼类生物学及渔业生物技术研究中心_期刊论文

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作者单位: 1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, 7 Donghu South Rd, Wuhan 430072, Hubei, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Univ Ottawa, Dept Biol, Ottawa, ON K1N 6N5, Canada
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