Loss of Inhibin Advances Follicle Activation and Female Puberty Onset but Blocks Oocyte Maturation in Zebrafish

Lu, H., Zhao, C., Zhu, B., Zhang, Z., Ge, W.
Endocrinology   161(12): (Journal)
Registered Authors
Ge, Wei
activin-inhibin-follistatin, follicle activation, folliculogenesis, oocyte maturation, ovary, puberty onset, zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Aromatase/metabolism
  • Female
  • Follicle Stimulating Hormone, beta Subunit/metabolism
  • Infertility, Female/genetics*
  • Infertility, Female/metabolism
  • Inhibins/genetics*
  • Inhibins/metabolism
  • Oocytes/metabolism*
  • Oogenesis/physiology*
  • Ovarian Follicle/metabolism
  • Ovary/metabolism*
  • Pituitary Gland/metabolism
  • Sexual Maturation/physiology*
  • Zebrafish/physiology*
33045050 Full text @ Endocrinology
Inhibin was first characterized in mammals as a gonadal dimeric protein that inhibited pituitary follicle-stimulating hormone (FSH) secretion. As in mammals, inhibin-specific α subunit (INHA/Inha/inha) has also been characterized in teleosts; however, its functions and physiological importance in fish reproduction remain unknown. Using CRISPR/Cas9 method, we generated an inha-deficient zebrafish line and analyzed its reproductive performance. As expected, pituitary expression of fshb increased significantly in both young and adult inha mutant. The expression of lhb also increased in the mutant, but only in sexually mature adults. Interestingly, the expression of activin βA (inhbaa) increased significantly in both ovary and testis of inha mutant and the expression of ovarian aromatase (cyp19a1a) also increased dramatically in the mutant ovary. The juvenile female mutant showed clear signs of early follicle activation or precocious puberty onset. However, the adult female mutant was infertile with follicles arrested at full-grown stage without final oocyte maturation and ovulation. Although follicle growth was overall normal in the mutant, the size and distribution of yolk granules in oocytes were distinct and some follicles showed granulosa cell hypertrophy. In contrast to females, inha null males showed normal spermatogenesis and fertility. As reported in mammals, we also found sporadic tumor formation in inha mutants. Taken together, our study not only confirmed some conserved roles of inhibin across vertebrates such as inhibition of FSH biosynthesis and tumor formation, but also revealed novel aspects of inhibin functions such as disruption of folliculogenesis and female infertility but no obvious involvement in spermatogenesis in fish.
Genes / Markers
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Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Engineered Foreign Genes
Errata and Notes