Minimal Fertility Defects in Mice Deficient in Oocyte-Expressed Smad4

ABSTRACT Bidirectional signaling between oocytes and granulosa cells is required for normal folliculogenesis. Oocyte-secreted members of the transforming growth factor beta (TGFB) family, growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) are well-known mediators of granulosa cell function. Deletion in granulosa cells of Smad4, the common SMAD mediating all canonical TGFB-related protein signals, results in infertility. Reciprocal signaling by granulosa cell-expressed TGFB family ligands, such as activin, to the oocyte during follicle development has been proposed but not tested in vivo using conditional knockout mice. Therefore, we generated two oocyte-specific conditional knockout models for the common SMAD, Smad4, using cre recombinase expression from either the zona pellucida 3 (Zp3) or Gdf9 promoter. Cre expression from the Gdf9 promoter occurs at a slightly earlier time point in follicle development than from Zp3. Deletion of Smad4 using Zp3cre had no effect on fertili...