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: Xiaohui Li, Swamy K Tripurani, Rebecca James, Stephanie A Pangas
• Journal: Biology of reproduction (Biol Reprod) Vol. 86 Issue 1 Pg. 1-6 (Jan 2012) ISSN: 1529-7268 [Electronic] United States
• PMID: 21900682 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Egg Proteins
• Gdf9 protein, mouse
• Growth Differentiation Factor 9
• Membrane Glycoproteins
• Receptors, Cell Surface
• Smad4 Protein
• Smad4 protein, mouse
• Zona Pellucida Glycoproteins
• Zp3 protein, mouse

Topics

• Animals
• Egg Proteins (genetics, metabolism)
• Female
• Fertility (genetics)
• Gene Expression Regulation (physiology)
• Granulosa Cells (metabolism)
• Growth Differentiation Factor 9 (genetics, metabolism)
• Membrane Glycoproteins (genetics, metabolism)
• Mice
• Mice, Knockout
• Oocytes (metabolism)
• Ovary (anatomy & histology, physiology)
• Ovulation (physiology)
• Promoter Regions, Genetic
• Receptors, Cell Surface (genetics, metabolism)
• Smad4 Protein (genetics, metabolism)
• Zona Pellucida Glycoproteins