The murine winged-helix transcription factor Foxl2 is required for granulosa cell differentiation and ovary maintenance

摘要: Human Blepharophimosis/ptosis/epicanthus inversus syndrome (BPES) type I is an autosomal dominant disorder associated with premature ovarian failure (POF) caused by mutations in FOXL2 , a winged-helix/forkhead domain transcription factor. Although it has been shown that is expressed adult ovaries, its function during folliculogenesis is not known. Here, we show the murine Foxl2 gene essential for granulosa cell differentiation and ovary maintenance. In lacZ homozygous mutant ovaries granulosa cells do complete squamous to cuboidal transition leading the absence of secondary follicles oocyte atresia. We further demonstrate that activin-βA anti-Mullerian inhibiting hormone expression absent or strongly diminished homozygous mutant ovaries. Unexpectedly, two weeks after birth most if all oocytes expressed Gdf9 indicating nearly primordial have already initiated at this stage. This activation, absence of functional granulosa cells, leads atresia progressive follicular depletion. In addition providing molecular mechanism premature ovarian BPES, these results suggest cell is not only crucial growth but also maintain follicular quiescence in vivo.