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泛素羧基末端水解酶L1 参与性成熟前小鼠卵母细胞的选择性剔除

顾艳琼, 陈秋菊, 顾正, 石燕, 姚余卫, 王健, 孙兆贵, 左嘉客

复旦大学上海医学院，上海 200032； 上海市计划生育科学研究所，国家人口和计划生育委员会计划生育药具重点实验室，上海 200032

摘要

异常卵母细胞的凋亡是性成熟前小鼠卵巢中具有缺陷的卵母细胞剔除的必要途径。泛素羧基末端水解酶L1 (ubiquitin carboxyl-terminal hydrolase L1, UCH-L1)参与构成的泛素依赖性蛋白降解系统通过降解特定蛋白调节细胞凋亡，而UCH-L1 依赖 性的细胞凋亡对于睾丸的生精作用是必要的。本文利用免疫组化技术考察了性成熟前小鼠卵巢中不同发育阶段的卵泡数目的变 化和UCH-L1 在卵母细胞中的表达情况，结果显示卵巢中卵泡总数在出生后第21 至28 天显著减少；而UCH-L1 蛋白在形态上 出现异常的卵母细胞中表达显著增强，可能以某种程度与Jab1 和p27Kip1 蛋白关联。免疫荧光共定位显示UCH-L1 在形态异常 的卵母细胞中密度较高，而Jab1 出现平行性的变化。免疫亲和分析显示卵巢中UCH-L1 和Jab1 发生作用。 以上结果提示， UCH-L1 在小鼠性成熟前的发育过程中异常卵母细胞的剔除方面具有重要作用，其作用可能以与Jab1 和p27Kip1 蛋白相关联的方 式发生。

关键词： 泛素羧基末端水解酶L1; p27Kip1; Jab1; 卵母细胞

分类号：R321.1

Ubiquitin carboxyl-terminal hydrolase L1 contributes to the oocyte selective elimination in prepubertal mouse ovaries

GU Yan-Qiong, CHEN Qiu-Ju, GU Zheng, SHI Yan, YAO Yu-Wei, WANG Jian, SUN Zhao-Gui, TSO Jia-Ke

Shanghai Medical College of Fudan University, Shanghai 200032, China； Key Laboratory of Contraceptive Drugs and Devices of National Population and Family Planning Commission of China, Shanghai Institute of Planned Parenthood Research, Shanghai 200032, China

Abstract

Apoptosis of abnormal oocytes is essential for defective oocyte elimination during prepubertal ovary development, and the ubiquitin system regulates the cell apoptosis via the degradation of specific proteins. Ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) is a component of the ubiquitin system, and the UCH-L1-dependent apoptosis is important for spermatogenesis. In the present study, the change in the number of follicles and the expression of UCH-L1 in oocytes were determined in prepubertal mouse ovaries by immunohistochemical techniques. A significant decrease in the follicular pool was found in prepubertal mouse ovaries during the period of day 21 to day 28 after birth, and accordingly, the UCH-L1 protein expression was increased, to some degree in association with Jun activation domain-binding protein 1 (Jab1) and cyclin-dependent kinase inhibitor p27Kip1. The increased UCH-L1 protein, together with the corresponding changes of Jab1 was detected in morphologically abnormal oocytes of prepubertal ovaries. Through the immunofluorescent colocalization, UCH-L1 was shown concentrating in abnormal oocytes, and a parallel change in Jab1 was also seen. The affinity analysis confirmed the interaction between UCH-L1 and Jab1 in ovaries. These results suggest that UCH-L1 plays an important role, possibly in association with Jab1 and p27Kip1, in selective elimination of abnormal oocytes during mouse prepubertal development.

Key words: ubiquitin carboxyl-terminal hydrolase L1; oocyte; p27Kip1; Jab1

收稿日期：2008-10-09　　录用日期：2009-02-19

通讯作者：孙兆贵　　E-mail: sunzg@sippr.stc.sh.cn

引用本文：

顾艳琼, 陈秋菊, 顾正, 石燕, 姚余卫, 王健, 孙兆贵, 左嘉客. 泛素羧基末端水解酶L1 参与性成熟前小鼠卵母细胞的选择性剔除 [J]. 生理学报 2009; 61 (2): 175-184.

GU Yan-Qiong, CHEN Qiu-Ju, GU Zheng, SHI Yan, YAO Yu-Wei, WANG Jian, SUN Zhao-Gui, TSO Jia-Ke. Ubiquitin carboxyl-terminal hydrolase L1 contributes to the oocyte selective elimination in prepubertal mouse ovaries. Acta Physiol Sin 2009; 61 (2): 175-184 (in Chinese with English abstract).