ABSTRACT: Germ-cell transcription factors control gene networks that regulate primordial follicle formation and oocyte differentiation during early, postnatal mouse oogenesis. Taking advantage of gene-edited mice lacking transcription factors expressed in female germ cells, we analyzed global gene expression profiles in perinatal ovaries from wildtype, FiglaNull, Lhx8Null and SohlhNull mice. Figla deficiency dysregulates expression of meiosis-related genes (e.g., Sycp3, Rad51 and Msy2) and a variety of genes (e.g., Nobox, Lhx8, Taf4b, Sohlh1, Sohlh2 and Gdf9) associated with oocyte growth and differentiation. The absence of FIGLA significantly impedes meiotic progression, causes DNA damage and results in oocyte apoptosis. Moreover, we find that FIGLA and other transcriptional regulators (e.g., NOBOX, LHX8, SOHLH1 and SOHLH2) are co-expressed in the same subset of germ cells in perinatal ovaries and Figla ablation dramatically disrupts KIT, NOBOX, LHX8, SOHLH1 and SOHLH2 expression. In addition, not only do FIGLA, SOHLH1 and LHX8 cross-regulate each other, they also cooperate by direct interaction with each during early oocyte development and share downstream gene targets. Thus, our findings substantiate a major role for FIGLA, LHX8 and SOHLH1 as multifunctional regulators of networks necessary for oocyte maintenance and differentiation during early folliculogenesis.
