Mettl3 Mutation Disrupts Gamete Maturation and Reduces Fertility in Zebrafish.

Xia, H., Zhong, C., Wu, X., Chen, J., Tao, B., Xia, X., Shi, M., Zhu, Z., Trudeau, V.L., Hu, W.
Genetics   208(2): 729-743 (Journal)
Registered Authors
Hu, Wei, Trudeau, V.L., Xia, Xiao-Qin, Zhu, Zuoyan
N6-methyladenosine, fertility, gamete maturation, mettl3, zebrafish
MeSH Terms
  • Adenosine/analogs & derivatives
  • Adenosine/chemistry
  • Adenosine/metabolism
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation/genetics*
  • Chromatography, Liquid
  • Female
  • Fertility*/genetics
  • Gene Deletion
  • Gene Expression
  • Gene Knockout Techniques
  • Germ Cells/metabolism*
  • Gonads/metabolism
  • Male
  • Methyltransferases/genetics*
  • Mutation*
  • Oocytes/metabolism
  • Spermatozoa/metabolism
  • Tandem Mass Spectrometry
  • Zebrafish/physiology*
29196300 Full text @ Genetics
N6-methyladenosine (m6A), catalyzed by Mettl3 methyltransferase, is a highly conserved epigenetic modification in eukaryotic messenger RNA (mRNA). Previous studies have implicated m6A modification in multiple biological processes, but the in vivo function of m6A 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, Zmettl3m/m , in zebrafish. We find that the oocytes in Zmettl3m/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 Zmettl3m/m adult males, we find defects in sperm maturation and sperm motility is significantly reduced. Further study shows that 11-ketotestosterone (11-KT) and 17β-estradiol (E2) levels are significantly decreased in Zmettl3m/m , and defective gamete maturation is accompanied by decreased overall m6A modification levels and disrupted expression of genes critical for sex hormone synthesis and gonadotropin signaling in Zmettl3m/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 m6A modifications are essential for optimal reproduction in vertebrates.
Genes / Markers
Show all Figures
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes