PUBLICATION

Disruption of Zebrafish Follicle-stimulating Hormone Receptor (fshr) but Not Luteinizing Hormone Receptor (lhcgr) Gene by TALEN Leads to Failed Follicle Activation in Females Followed by Sexual Reversal to Males

Authors
Zhang, Z., Lau, S.W., Zhang, L., Ge, W.
ID
ZDB-PUB-150521-1
Date
2015
Source
Endocrinology   156(10): 3747-62 (Journal)
Registered Authors
Ge, Wei, Zhang, Zhiwei
Keywords
none
MeSH Terms
  • Animals
  • Cells, Cultured
  • Disorders of Sex Development/embryology
  • Disorders of Sex Development/genetics*
  • Disorders of Sex Development/metabolism
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism
  • Female
  • Fertility/genetics
  • Follicle Stimulating Hormone/metabolism
  • Gene Knockout Techniques/methods
  • Luteinizing Hormone/metabolism
  • Male
  • Mutation
  • Ovarian Follicle/cytology
  • Ovarian Follicle/embryology
  • Ovarian Follicle/metabolism*
  • Receptors, FSH/genetics*
  • Receptors, FSH/metabolism
  • Receptors, LH/genetics*
  • Receptors, LH/metabolism
  • Sex Factors
  • Testis/embryology
  • Testis/metabolism
  • Time Factors
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed
25993524 Full text @ Endocrinology
Abstract
Gonadotropins are primary hormones that control vertebrate reproduction. In a recent study, we analyzed the impacts of FSH and LH on zebrafish reproduction by disrupting FSH and LH β genes (fshb and lhb) using TALEN technology. Using the same approach, we successfully deleted FSH and LH receptor genes (fshr and lhcgr) in the present study. In contrast to the deficiency of its cognate ligand FSH, the fshr-deficient females showed a complete failure of follicle activation with all ovarian follicles arrested at the PG-PV (primary growth-previtellogenic) transition, which is the marker for puberty onset in females. Interestingly, after blockade at the PG stage for varying times, all females reversed to males, and all these males were fertile. In fshr-deficient males, spermatogenesis was normal in adults, but the initiation of spermatogenesis in juveniles was retarded. In contrast to fshr, the deletion of lhcgr gene alone caused no obvious phenotypes in both males and females; however, double mutation of fshr and lhcgr resulted in infertile males. In summary, our results in the present study showed that Fshr was indispensable to folliculogenesis and the disruption of fshr gene resulted in a complete failure of follicle activation followed by masculinization into males. In contrast, lhcgr does not seem to be essential to zebrafish reproduction in both males and females. Neither Fshr nor Lhcgr deficiency could phenocopy the deficiency of their cognate ligands FSH and LH, which is likely due to the fact that Fshr can be activated by both FSH and LH in the zebrafish.
Genes / Markers
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping