Male infertility is closely associated with spermatogenesis disorders triggered by aberrant gene expression or abnormal signaling pathways in the testis. The mammalian target of rapamycin (mTOR) is a central regulator of cell metabolism, playing an important role in regulating cell proliferation, differentiation, translation, actin polymerization, cycle progression, energy metabolism, autophagy, and other cellular activities. PI3K-Akt and LKB1-AMPK, the two well-defined classic signal transduction pathways, regulate the expressions of mTOR and its downstream p70S6K/4EBP1 through different molecular pathways. Recent studies show that mTOR-p70S6K/4EBP1 signaling participates in the regulation of the proliferation and differentiation of testicular cells and spermatogenesis. This review focuses on the role of PI3K-Akt/LKB1- AMPK-mTOR signaling cascades in testis development and spermatogenesis, providing some new perspectives for the studies of the molecular mechanism underlying male sterility.
男性不育与睾丸组织基因表达异常或信号传导异常所致的生精障碍密切相关。哺乳动物雷帕霉素靶蛋白(mTOR)是细胞代谢的中枢调节器,在细胞增殖、分化、翻译、肌动蛋白聚合、细胞周期、能量代谢和自噬等细胞活动中起重要调控作用。PI3K-Akt和LKB1-AMPK这两条经典信号通路可通过不同分子路径调节mTOR信号及其下游靶蛋白p70S6K/4EBP1的表达。近来研究表明mTOR-p70S6K/4EBP1信号分子参与调节睾丸细胞增殖、分化和精子形成,本综述就PI3K-Akt/LKB1-AMPK-mTOR信号级联反应机制在睾丸发育和精子发生过程中的作用进行概述,为男性不育分子机制研究提供新观点及新思路。.
Keywords: mammalian target of rapamycin; signaling pathway; spermatogenesis; testicular development.