Germ cells in the teleost fish medaka have an inherent feminizing effect

Germ cells give rise to eggs or sperm. However, recent analyses in medaka (Oryzias latipes) showed that germ cells are also important for feminization of gonads, although this novel role of germ cells has not been characterized in detail. Here, we show that the feminizing effect is inherent to germ cells and is not affected by gametogenic stages or the sexual fate of germ cells. Three medaka mutants were generated to demonstrate this effect: figlα mutants, in which follicle formation is disrupted; meioC mutants, in which germ cells are unable to commit to gametogenesis and meiosis; and dazl mutants, in which germ cells do not develop into gonocytes. All these different stages of germ cells in XX mutants have an ability to feminize the gonads, resulting in the formation of gonads with ovarian structures. In addition to normal ovarian development, we also suggest that the increased number of gonocytes is sufficient for male to female sex reversal in XY medaka. These results may genetically demonstrate that the mechanism underlying the feminizing effect of germ cells is activated before the sexual fate decision of germ cells and meiosis, probably by the time of gonocyte formation in medaka. AUTHOR SUMMARY: Germ cells are the only cells that can transfer genetic materials to the next generation via the sperm or egg. However, recent analyses in teleosts revealed another essential role of germ cells: feminizing the gonads. In our study, medaka mutants in which gametogenesis was blocked at specific stages provides the novel view that the feminizing effect of germ cells occurs in parallel with other reproductive elements, such as meiosis, the sexual fate decision of germ cells, and gametogenesis. Germ cells in medaka may have a potential to feminize gonads at the moment they have developed.