The Sperm Laboratory, College of Life Sciences, Zhejiang University, 310058, Hangzhou, Zhejiang, China.
Cell Death Dis. 2019 Jul 17;10(8):541. doi: 10.1038/s41419-019-1782-z.
The functions of Sertoli cells in spermatogenesis have attracted much more attention recently. Normal spermatogenesis depends on Sertoli cells, mainly due to their influence on nutrient supply, maintenance of cell junctions, and support for germ cells' mitosis and meiosis. Accumulating evidence in the past decade has highlighted the dominant functions of the MAPK, AMPK, and TGF-β/Smad signaling pathways during spermatogenesis. Among these pathways, the MAPK signaling pathway regulates dynamics of tight junctions and adherens junctions, proliferation and meiosis of germ cells, proliferation and lactate production of Sertoli cells; the AMPK and the TGF-β/Smad signaling pathways both affect dynamics of tight junctions and adherens junctions, as well as the proliferation of Sertoli cells. The AMPK signaling pathway also regulates lactate supply. These signaling pathways combine to form a complex regulatory network for spermatogenesis. In testicular tumors or infertile patients, the activities of these signaling pathways in Sertoli cells are abnormal. Clarifying the mechanisms of signaling pathways in Sertoli cells on spermatogenesis provides new insights into the physiological functions of Sertoli cells in male reproduction, and also serves as a pre-requisite to identify potential therapeutic targets in abnormal spermatogenesis including testicular tumor and male infertility.
近年来,支持细胞在精子发生中的功能引起了更多的关注。正常的精子发生依赖于支持细胞,这主要是由于它们对营养物质供应、细胞连接的维持以及对精母细胞有丝分裂和减数分裂的支持的影响。在过去十年中,越来越多的证据强调了 MAPK、AMPK 和 TGF-β/Smad 信号通路在精子发生中的主导作用。在这些通路中,MAPK 信号通路调节紧密连接和黏附连接的动态、精母细胞的增殖和减数分裂、支持细胞的增殖和乳酸产生;AMPK 和 TGF-β/Smad 信号通路都影响紧密连接和黏附连接的动态以及支持细胞的增殖。AMPK 信号通路还调节乳酸的供应。这些信号通路共同构成了精子发生的复杂调控网络。在睾丸肿瘤或不育患者中,支持细胞中这些信号通路的活性异常。阐明支持细胞中信号通路对精子发生的作用机制,为支持细胞在男性生殖中的生理功能提供了新的认识,也为鉴定睾丸肿瘤和男性不育等异常精子发生中的潜在治疗靶点提供了前提条件。