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(英文)

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

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。

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 carboxyt-terminal hydrolase L1 （UCH- L1） is a component of the ubiquitin system, and the UCH-Ll-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 （Jabl） and cyclin-dependent kinase inhibitor p27Kip1. The increased UCH-L1 protein, together with the corresponding changes of Jabl 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 Jabl was also seen. The affinity analysis confirmed the interaction between UCH-L1 and Jabl in ovaries. These results suggest that UCH-L1 plays an important role, possibly in association with Jabl and p27kip1, in selective elimination of abnormal oocytes during mouse prepubertal development.