PUBLICATION

Loss of growth differentiation factor 9 causes an arrest of early folliculogenesis in zebrafish-A novel insight into its action mechanism

Authors
Chen, W., Zhai, Y., Zhu, B., Wu, K., Fan, Y., Zhou, X., Liu, L., Ge, W.
ID
ZDB-PUB-221216-26
Date
2022
Source
PLoS Genetics   18: e1010318e1010318 (Journal)
Registered Authors
Chen, Weiting, Fan, Yuqin, Ge, Wei, Zhu, Bo
Keywords
none
MeSH Terms
  • Activins/genetics
  • Activins/metabolism
  • Animals
  • Female
  • Growth Differentiation Factor 9*/genetics
  • Growth Differentiation Factor 9*/metabolism
  • Inhibins/genetics
  • Inhibins/metabolism
  • Male
  • Mice
  • Ovarian Follicle/metabolism
  • Zebrafish*/genetics
  • Zebrafish*/metabolism
PubMed
36520929 Full text @ PLoS Genet.
Abstract
Growth differentiation factor 9 (GDF9) was the first oocyte-specific growth factor identified; however, most information about GDF9 functions comes from studies in the mouse model. In this study, we created a mutant for Gdf9 gene (gdf9-/-) in zebrafish using TALEN approach. The loss of Gdf9 caused a complete arrest of follicle development at primary growth (PG) stage. These follicles eventually degenerated, and all mutant females gradually changed to males through sex reversal, which could be prevented by mutation of the male-promoting gene dmrt1. Interestingly, the phenotypes of gdf9-/- could be rescued by simultaneous mutation of inhibin α (inha-/-) but not estradiol treatment, suggesting a potential role for the activin-inhibin system or its signaling pathway in Gdf9 actions. In gdf9 null follicles, the expression of activin βAa (inhbaa), but not βAb (inhbab) and βB (inhbb), decreased dramatically; however, its expression rebounded in the double mutant (gdf9-/-;inha-/-). These results indicate clearly that the activation of PG follicles to enter the secondary growth (SG) requires intrinsic factors from the oocyte, such as Gdf9, which in turn works on the neighboring follicle cells to trigger follicle activation, probably involving activins. In addition, our data also support the view that estrogens are not involved in follicle activation as recently reported.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping