PUBLICATION

Igf3 is essential for ovary differentiation in zebrafish†

Authors
Xie, Y., Huang, D., Chu, L., Liu, Y., Sun, X., Li, J., Cheng, C.H.K.
ID
ZDB-PUB-201208-32
Date
2020
Source
Biology of reproduction   104(3): 589-601 (Journal)
Registered Authors
Keywords
Igf3, estrogen, ovary development, sex differentiation, sex reversal
MeSH Terms
  • Animals
  • Apoptosis
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Developmental/physiology*
  • Male
  • Mutation
  • Oocytes/growth & development
  • Ovary/growth & development*
  • Sex Differentiation/physiology*
  • Somatomedins/genetics
  • Somatomedins/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
33276384 Full text @ Biol. Reprod.
Abstract
Zebrafish gonadal sexual differentiation is an important but poorly understood subject. Previously, we have identified a novel Igf named Igf3 in teleosts. The importance of Igf3 in oocyte maturation and ovulation has been recently demonstrated by us in zebrafish. In this study, we have further found the essential role of Igf3 in gonadal sexual differentiation of zebrafish. A differential expression pattern of igf3 between ovary and testis during sex differentiation (higher level in ovary than in testis) was found in zebrafish. An igf3 knockout zebrafish line was established using TALENs-mediated gene knockout technique. Intriguingly, all igf3 homozygous mutants were males due to the female-to-male sex reversal occurred during sex differentiation. Further analysis showed that Igf3 did not seem to affect the formation of so-called juvenile ovary and oocyte-like germ cells. Oocyte development was arrested at primary growth stage, and the ovary was gradually sex-reversed to testis before 60 dpf. Such sex reversal was likely due to decreased germ cell proliferation by suppressing PI3K/Akt pathway in early ovaries of igf3 mutants. Estrogen is considered as a master regulator in fish sex differentiation. Here, we found that igf3 expression could be up-regulated by estrogen in early stages of ovarian follicles as evidenced in in vitro treatment assays and cyp19a1a mutant zebrafish, and E2 failed to rescue the defects of igf3 mutants in ovarian development, suggesting that Igf3 may serve as a downstream factor of estrogen signaling in sex differentiation. Taken together, we demonstrated that Igf3 is essential for ovary differentiation in zebrafish.
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