Expression relationship of Hippo signaling molecules and ovarian germline stem cell markers in the ovarian aging process of women and mice
- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 3
- DOI:
- 10.13294/j.aps.2019.0034
- Key Word:
- 功能状态卵巢;卵巢衰退模型;卵巢生殖干细胞;Hippo通路
Abstract： 本研究旨在探讨Hippo信号通路的主要分子与卵巢生殖干细胞(ovarian germline stem cell,OGSC)相关因子在人和小鼠衰老不同功能状态卵巢中表达的相关性.选择2月龄性成熟期(正常对照)、12月龄衰老期(生理性衰退)KM系小鼠卵巢,以及青年期(青春期后～35岁)、中年期(36～50岁)和绝经期(51～60岁)女性卵巢皮层样本;采用环磷酰胺/马利兰片(cyclophosphamide/busulfan,CY/BUS)腹腔注射方式构建小鼠病理性衰退卵巢模型,用HE染色法检测各级卵泡的变化,用免疫组织化学法和免疫荧光染色法检测Hippo信号分子与OGSC相关因子(MVH/OCT4)的定位和表达变化,用Western blot检测Hippo信号通路的主要分子和OGSC相关因子的蛋白表达水平.结果 显示,在生理性和病理性衰退模型小鼠卵巢中已无正常卵泡,仅有一些闭锁卵泡存在;和正常对照小鼠相比,生理性和病理性衰退模型小鼠卵巢皮层Hippo信号通路的主要分子(pYAPl)和MVH/OCT4蛋白表达水平均显著降低,病理性衰退模型小鼠卵巢皮层pYAP l/YAP1比值升高.和青年期女性相比,中年期和绝经期女性卵巢表面上皮(ovarian surface epithelium,OSE)结构逐渐变得松散,皮层处细胞也逐渐减少;LATS2蛋白表达水平在青年期女性OSE最高,MST1蛋白表达水平在老年期女性OSE最低,而YAP1和pYAP1蛋白表达水平在中年期女性OSE最高;相比青年期女性,中年期和老年期OSE的pYAP1/YAPl比值显著降低,而二者之间无显著性差异.青年期女性OSE中MVH蛋白表达水平显著高于中年期和老年期.以上结果表明,Hippo信号通路的主要分子与OGSC相关因子的蛋白表达之间有相关性,提示Hippo信号通路可能调控OGSC相关因子表达,从而参与卵巢功能的生理性衰退和病理性衰退过程.
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