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The inhibition of WIP1 phosphatase accelerates the depletion of primordial follicles
Reproductive BioMedicine Online ( IF 4 ) Pub Date : 2021-05-19 , DOI: 10.1016/j.rbmo.2021.05.007
Su Zhou 1 , Yueyue Xi 1 , Yingying Chen 1 , Tong Wu 1 , Wei Yan 1 , Milu Li 1 , Meng Wu 1 , Aiyue Luo 1 , Wei Shen 1 , Tao Xiang 1 , Shixuan Wang 1
Affiliation  

Research question

What role does wild-type p53-induced phosphatase 1 (WIP1) play in the regulation of primordial follicle development?

Design

WIP1 expression was detected in the ovaries of mice of different ages by western blotting and immunohistochemical staining. Three-day-old neonatal mouse ovaries were cultured in vitro with or without the WIP1 inhibitor GSK2830371 (10 μM) for 4 days. Ovarian morphology, follicle growth and follicle classification were analysed and the PI3K–AKT–mTOR signal pathway and the WIP1–p53-related mitochondrial apoptosis pathway evaluated.

Results

WIP1 expression was downregulated with age. Primordial follicles were significantly decreased in the GSK2830371-treated group, without a significant increase in growing follicles. The ratio of growing follicles to primordial follicles was not significantly different between the control and GSK2830371 groups, and no significant variation was observed in the PI3K–AKT–mTOR signal pathway. The inhibition of WIP1 phosphatase accelerated primordial follicle atresia by activating the p53–BAX–caspase-3 pathway.

Conclusions

These findings reveal that WIP1 participates in regulating primordial follicle development and that inhibiting WIP1 phosphatase leads to massive primordial follicle loss via interaction with the p53–BAX–caspase-3 pathway. This might also provide valuable information for understanding decreased ovarian reserve during ovarian ageing.



中文翻译:

WIP1磷酸酶的抑制加速了原始卵泡的消耗

研究问题

野生型 p53 诱导的磷酸酶 1 (WIP1) 在调节原始卵泡发育中起什么作用?

设计

通过蛋白质印迹和免疫组织化学染色检测不同年龄小鼠卵巢中WIP1的表达。三天大的新生小鼠卵巢在体外培养4 天,有或没有 WIP1 抑制剂 GSK2830371 (10 μM)。分析了卵巢形态、卵泡生长和卵泡分类,并评估了 PI3K-AKT-mTOR 信号通路和 WIP1-p53 相关的线粒体凋亡通路。

结果

WIP1 表达随着年龄的增长而下调。GSK2830371治疗组的原始卵泡显着减少,生长卵泡没有显着增加。对照组和 GSK2830371 组的生长卵泡与原始卵泡的比例无显着差异,PI3K-AKT-mTOR 信号通路未观察到显着变化。WIP1 磷酸酶的抑制通过激活 p53-BAX-caspase-3 通路加速了原始卵泡闭锁。

结论

这些发现表明,WIP1 参与调节原始卵泡发育,抑制 WIP1 磷酸酶通过与 p53-BAX-caspase-3 途径的相互作用导致大量原始卵泡丢失。这也可能为了解卵巢衰老过程中卵巢储备减少提供有价值的信息。

更新日期:2021-07-28
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