Deng Chun-Yan, Lv Mei, Luo Bin-Han, Zhao Si-Ze, Mo Zhong-Cheng, Xie Yuan-Jie
Clinical Anatomy & Reproductive Medicine Application Institute, Department of Histology and Embryology, Hengyang Medical School, University of South China, Hengyang 421001, China.
Faculty of Basic Medical Sciences, Guilin Medical University, Guangxi, China.
Curr Mol Med. 2021;21(7):539-548. doi: 10.2174/1566524020666201203164910.
Male fertility is closely related to the normal function of the hypothalamicpituitary- testicular axis. The testis is an important male reproductive organ that secretes androgen and produces sperm through spermatogenesis. Spermatogenesis refers to the process by which spermatogonial stem cells (SSCs) produce highly differentiated spermatozoa and is divided into three stages: mitosis, meiosis and spermiogenesis. Spermatogenesis requires SSCs to strike a proper balance between self-renewal and differentiation and the commitment of spermatocytes to meiosis, which involves many molecules and signalling pathways. Abnormal gene expression or signal transduction in the hypothalamus and pituitary, but particularly in the testis, may lead to spermatogenic disorders and male infertility. The phosphoinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway is involved in many stages of male reproduction, including the regulation of the hypothalamus-pituitarygonad (HPG) axis during spermatogenesis, the proliferation and differentiation of spermatogonia and somatic cells, and the regulation of sperm autophagy and testicular endocrine function in the presence of environmental pollutants, particularly endocrinedisrupting chemicals (EDCs). In the PI3K/AKT/mTOR signalling pathway, mTOR is considered the central integrator of several signals, regulating metabolism, cell growth and proliferation. In particular, mTOR plays an important role in the maintenance and differentiation of SSCs, as well as in regulating the redox balance and metabolic activity of Sertoli cells, which play an important role in nutritional support during spermatogenesis.
男性生育能力与下丘脑 - 垂体 - 睾丸轴的正常功能密切相关。睾丸是重要的男性生殖器官，它分泌雄激素并通过精子发生过程产生精子。精子发生是指精原干细胞（SSCs）产生高度分化精子的过程，分为三个阶段：有丝分裂、减数分裂和精子形成。精子发生需要精原干细胞在自我更新和分化之间取得适当平衡，以及精母细胞进入减数分裂，这涉及许多分子和信号通路。下丘脑和垂体，尤其是睾丸中基因表达或信号转导异常，可能导致生精障碍和男性不育。磷脂酰肌醇 - 3 - 激酶（PI3K）/蛋白激酶B（AKT）/雷帕霉素靶蛋白（mTOR）信号通路参与男性生殖的许多阶段，包括精子发生过程中下丘脑 - 垂体 - 性腺（HPG）轴的调节、精原细胞和体细胞的增殖与分化，以及在存在环境污染物，特别是内分泌干扰化学物质（EDCs）的情况下对精子自噬和睾丸内分泌功能的调节。在PI3K/AKT/mTOR信号通路中，mTOR被认为是多种信号的中央整合器，调节代谢、细胞生长和增殖。特别是，mTOR在精原干细胞的维持和分化中起重要作用，以及在调节支持精子发生过程中营养支持的支持细胞的氧化还原平衡和代谢活性方面也起重要作用。
