Regulation of primordial follicle recruitment by cross-talk between the Notch and phosphatase and tensin homologue (PTEN)/AKT pathways.
Regulation of primordial follicle recruitment by cross-talk between the Notch and phosphatase and tensin homologue (PTEN)/AKT pathways.
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DOI：
10.1071/rd14212
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发表时间：
2016-05
期刊：
影响因子：
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通讯作者：
Lin-Qing Wang;Jing-Cai Liu;Chun-Lei Chen;Shun-Feng Cheng;Xiaofeng Sun;Yong Zhao;S. Yin;Zhu-Mei Hou-Zh
中科院分区：
文献类型：
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作者：
Lin-Qing Wang;Jing-Cai Liu;Chun-Lei Chen;Shun-Feng Cheng;Xiaofeng Sun;Yong Zhao;S. Yin;Zhu-Mei Hou-Zh
卵母细胞的生长和卵泡的发育需要参与细胞增殖和存活的某些途径，例如磷脂酰肌醇3-激酶（PI 3 K）途径和Notch信号传导途径。本研究的目的是探讨Notch和PI 3 K/AKT信号通路之间的相互作用及其对原始卵泡募集的影响。当L-685，458或N-[N-（3，5-二氟苯乙酰基）-1-丙氨酰]-S-苯基甘氨酸丁酯（DAPT）在体外抑制Notch通路时，小鼠卵巢中Notch通路基因的表达和生长卵泡中卵母细胞的百分比显著降低。到产后2天，暴露于DAPT、针对Notch 1的短干扰（si）RNA或针对Hairy和分裂增强子-1（Hes 1）的siRNA的卵巢显著降低了HES 1（Notch信号通路的靶蛋白）的表达。与此相反，磷酸酶和张力蛋白同源物（Pten），AKT信号通路的负调节，表达显着增加。免疫共沉淀法（Co-IP）显示HES 1和PTEN之间存在相互作用。此外，Notch信号通路的抑制抑制AKT磷酸化和颗粒细胞的增殖。总之，原始卵泡的募集受到颗粒细胞增殖和Notch和PI 3 K/AKT信号通路之间相互作用的调节的影响。
The growth of oocytes and the development of follicles require certain pathways involved in cell proliferation and survival, such as the phosphatidylinositol 3-kinase (PI3K) pathway and the Notch signalling pathway. The aim of the present study was to investigate the interaction between Notch and the PI3K/AKT signalling pathways and their effects on primordial follicle recruitment. When the Notch pathway was inhibited by L-685,458 or N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycinet-butyl ester (DAPT) in vitro, the expression of genes in the pathway and the percentage of oocytes in growing follicles decreased significantly in mouse ovaries. By 2 days postpartum, ovaries exposed to DAPT, short interference (si) RNA against Notch1 or siRNA against Hairy and enhancer of split-1 (Hes1) had significantly decreased expression of HES1, the target protein of the Notch signalling pathway. In contrast, expression of phosphatase and tensin homologue (Pten), a negative regulator of the AKT signalling pathway, was increased significantly. Co immunoprecipitation (Co-IP) revealed an interaction between HES1 and PTEN. In addition, inhibition of the Notch signalling pathway suppressed AKT phosphorylation and the proliferation of granulosa cells. In conclusion, the recruitment of primordial follicles was affected by the proliferation of granulosa cells and regulation of the interaction between the Notch and PI3K/AKT signalling pathways.