Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice
Hippo Signaling Pathway Reveals a Spatio-Temporal Correlation with the Size of Primordial Follicle Pool in Mice
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Hippo 信号通路揭示了小鼠原始卵泡池大小的时空相关性
DOI：
10.1159/000369752
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发表时间：
2015-01-01
影响因子：
--
通讯作者：
Zheng, Liping
中科院分区：
文献类型：
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作者：
Xiang, Cheng;Li, Jia;Zheng, Liping
背景资料：Hippo信号通路是一种高度保守的细胞信号系统，存在于大多数多细胞生物中，调节细胞增殖、分化和凋亡。已有报道Hippo信号通路成员在哺乳动物卵巢中表达，但该通路在原始卵泡发育中的确切功能尚不清楚。研究方法：为分析Hippo通路核心成分与原始卵泡池大小的时空相关性，采用Western blot、Real-time PCR和免疫组织化学方法，检测了MST 1、LATS 2和YAP 1 mRNA和蛋白在生后3 d、1 m、5 m、16 m小鼠卵巢和小鼠原始卵泡体外培养模型中的表达和定位。结果如下：MST 1和LATS 2的蛋白和mRNA表达均随鼠龄的增加而显著降低而雅普的表达则呈相反趋势，p雅普的蛋白表达在1个月前显著增加，之后没有观察到显著变化。p雅普/雅普比值明显降低。卵巢体外培养8d后，生后3d小鼠卵巢中原始卵泡被激活，并发育为初级卵泡，PCNA表达显著增加（p < 0.05）。MST和LATS的mRNA和蛋白表达均显著降低（p < 0.05），雅普的表达显著升高（p < 0.05，p < 0.01），p雅普/雅普比值显著降低（p < 0.05）。结论：以上结果表明，Hippo信号通路的核心组分在小鼠卵泡发育过程中，尤其是原始卵泡体外激活前后的表达发生了变化。原始卵泡的激活可能与pYAP 1/YAP 1比值的显著降低有关。结论：Hippo信号通路在小鼠卵巢中表达，并与原始卵泡池大小存在时空相关性。
Background: The Hippo signaling pathway, a highly conserved cell signaling system, exists in most multicellular organisms and regulates cell proliferation, differentiation, and apoptosis. It has been reported that the members of Hippo signaling are expressed in mammalian ovaries, but the exact functions of this pathway in primordial follicle development remains unclear. Methods: To analyze the spatio-temporal correlation between the core component of Hippo pathway and the size of primordial follicle pool, Western blot, Real-time PCR and immunohistochemistry were used, and the expression and localization of MST1, LATS2 and YAP1 mRNA and protein were examined in 3 d, 1 m, 5 m, 16 m postnatal mice ovary and the culture model of mice primordial follicle in vitro. Results: Both the protein and mRNA expression of the MST1 and LATS2 were decreased significantly as mouse age increased (p < 0.05), however, the mRNA expression of them increased significantly in 16 m compared with 5 m as well as the protein expression of LATS2.The expression of YAP showed the opposite trend, and the significant protein expression of pYAP was increased before 1 m, after which no significant change was observed. Moreover, the ratio of pYAP/YAP decreased significantly. Culturing ovaries for 8 d in vitro resulted in the activation of primordial follicles in 3 d postnatal mice ovaries, and these developed into primary follicles with the expression of PCNA increasing significantly (p < 0.05). The mRNA and protein expression of MST and LATS decreased significantly (p < 0.05), and the expression of YAP increased significantly (p < 0.05, p < 0.01), whereas the ratio of pYAP/YAP decreased significantly (p < 0.05). Conclusion: The above results reveal that the expression of the core components of Hippo pathway changed during mouse follicular development, especially before and after primordial follicle activation in vitro. The primordial follicle activation may be related to the significant decrease of the ratio of pYAP1/YAP1. In conclusion, Hippo signaling pathway expressed in mice ovaries and have spatio-temporal correlation with the size of primordial follicle pool.