title: 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 fertility, while deletion of Smad4 with Gdf9icre resulted in a slight, but significant, reduction in litter size. These mouse models suggest a novel, although minor, role for Smad4 in the oocyte restricted to the primordial follicle stage.
authors: Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
authors: Xiaohui
authors: X
authors: Li
authors: Swamy K
authors: SK
authors: Tripurani
authors: Rebecca
authors: R
authors: James
authors: Stephanie A
authors: SA
authors: Pangas
mesh_terms: D000818:Animals; D004527:Egg Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology; D006107:Granulosa Cells / Q000378:metabolism; D055429:Growth Differentiation Factor 9 / Q000235:genetics / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism*; D010053:Ovary / Q000033:anatomy & histology / Q000502:physiology; D010060:Ovulation / Q000502:physiology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D000072216:Zona Pellucida Glycoproteins
chemical_list: D004527:Egg Proteins; C525898:Gdf9 protein, mouse; D055429:Growth Differentiation Factor 9; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D000072216:Zona Pellucida Glycoproteins; C000606521:Zp3 protein, mouse