Minimal Fertility Defects in Mice Deficient in Oocyte-Expressed Smad4
Minimal Fertility Defects in Mice Deficient in Oocyte-Expressed Smad4
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DOI：
10.1095/biolreprod.111.094375
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发表时间：
2012-01-01
影响因子：
3.6
通讯作者：
Pangas, Stephanie A.
中科院分区：
文献类型：
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作者：
Li, Xiaohui;Tripurani, Swamy K.;Pangas, Stephanie A.
卵母细胞和颗粒细胞之间的双向信号传导是正常卵泡发生所必需的。卵母细胞分泌的转化生长因子β（TGFB）家族成员、生长分化因子9（GDF 9）和骨形态发生蛋白15（BMP 15）是众所周知的颗粒细胞功能介质。Smad4是一种常见的SMAD，介导所有典型的TGF β相关蛋白信号，其在颗粒细胞中的缺失导致不育。已经提出了在卵泡发育过程中由颗粒细胞表达的TGFB家族配体（如激活素）向卵母细胞的相互信号传导，但未使用条件性基因敲除小鼠在体内进行测试。因此，我们产生了两个卵母细胞特异性条件敲除模型的共同SMAD，Smad4，使用cre重组酶表达从透明质酸3（Zp3）或Gdf9启动子。Cre表达从Gdf9启动子发生在略早的时间点在卵泡发育比从Zp3。使用Zp3cre删除Smad4对生育力没有影响，而使用Gdf9icre删除Smad4导致窝仔数轻微但显著减少。这些小鼠模型表明，Smad4在卵母细胞中的作用仅限于原始卵泡阶段，但作用较小。
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.