Ovarian aromatase loss-of-function mutant medaka undergo ovary degeneration and partial female-to-male sex reversal after puberty

Mol Cell Endocrinol. 2018 Jan 15;460:104-122. doi: 10.1016/j.mce.2017.07.013. Epub 2017 Jul 13.


Although estrogens have been generally considered to play a critical role in ovarian differentiation in non-mammalian vertebrates, the specific functions of estrogens during ovarian differentiation remain unclear. We isolated two mutants with premature stops in the ovarian aromatase (cyp19a1) gene from an N-ethyl-N-nitrosourea-based gene-driven mutagenesis library of the medaka, Oryzias latipes. In XX mutants, gonads first differentiated into normal ovaries containing many ovarian follicles that failed to accumulate yolk. Subsequently, ovarian tissues underwent extensive degeneration, followed by the appearance of testicular tissues on the dorsal side of ovaries. In the newly formed testicular tissue, strong expression of gsdf was detected in sox9a2-positive somatic cells surrounding germline stem cells suggesting that gsdf plays an important role in testicular differentiation during estrogen-depleted female-to-male sex reversal. We conclude that endogenous estrogens synthesized after fertilization are not essential for early ovarian differentiation but are critical for the maintenance of adult ovaries.

Keywords: Aromatase; Estrogens; Ovarian differentiation; Sex plasticity; Teleost fish; cyp19a1.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aromatase / chemistry
  • Aromatase / genetics
  • Base Sequence
  • Cell Lineage
  • Down-Regulation / genetics
  • Estrogens / biosynthesis
  • Female
  • Gene Expression Profiling
  • Loss of Function Mutation / genetics*
  • Male
  • Oryzias / genetics*
  • Ovarian Follicle / pathology
  • Ovary / pathology*
  • Sex Determination Processes* / genetics
  • Sexual Maturation*
  • Testis / pathology
  • Up-Regulation / genetics
  • Vitellogenins / metabolism


  • Estrogens
  • Vitellogenins
  • Aromatase