A compromised gsdf signaling leads to gamatogenesis confusion and subfertility in medaka

Summary statement Gsdf signals trigger the gamatogenesis, alter the somatic expression of Fsh/Lh receptors and brain type aromatase in medaka brain and gonad. Gonadal soma-derived factor ( gsdf ) and anti-Mullerian hormone ( amh ) are somatic male determinants in several species of teleosts, although the mechanisms by which they trigger the indifferent germ cells into the male pathway remain unknown. This study aimed to decipher the roles of gsdf/amh in directing the sexual fate of germ cells using medaka as a model. Transgenic lines (Tg cryG ) that restrictively and persistently express a Gsdf-Gfp fusion protein in the lens and the hypothalamus-pituitary-gonad (HPG) axis, were generated under the control of a mouse γF-crystallin promoter. A high frequency (44.4%) of XX male sex reversals was obtained in Tg cryG lines, indicating that signals of gsdf-expressing cells in HPG were enough for the spermatogenesis activation in the genetic females. Furthermore, all Tg cryG XY individuals with endogenous gsdf depletion (named Sissy ) displayed intersex (100%) with enlarged ovotestis in contrast to a giant ovary developed in XY gsdf deficiency. The heterogeneous expression of gsdf led to the confusion of gamatogenesis and ovotestis development, similar to some hotei (amhr2 ) mutants, suggests that the signaling balance of gsdf/amh is essential for proper gamatogenesis, maintaining sex steroid production and gonadotropin secretion, which are evolutionarily conserved across phyla .