WNT signaling in ovarian follicle biology and tumorigenesis.

The WNTS are an expansive family of glycoprotein signaling molecules known mostly for the roles they play in embryonic development. WNT signaling first caught the attention of ovarian biologists when it was reported that the inactivation of Wnt4 in mice results in partial female-to-male sex reversal and oocyte depletion. More recently, studies using loss- and gain-of-function transgenic mouse models demonstrated the requirement for Wnt4, Fzd4 and Ctnnb1, components of the WNT pathway, for normal folliculogenesis, luteogenesis and steroidogenesis, and showed that dysregulated WNT signaling can cause granulosa cell tumor development. This review covers our current knowledge of WNT signaling in ovarian follicles, highlighting both the great promise and the many unresolved questions of this emerging field of research.