Multiple signaling pathways in Sertoli cells: recent findings in spermatogenesis

Abstract

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.

Single-cell analysis of developing and azoospermia human testicles reveals central role of Sertoli cells

“…From a metabolic perspective, we observed that once a cell enters Stage_b, its preferred metabolic pathway changes from oxidative phosphorylation to glycolysis. This is consistent with the previous observation that lactic acid (produced by glycolysis) provides energy for germ cell development 26 . It is worth noting that all three stages of Sertoli cells exist and form a steady state in adult testes, maintaining the basic structure of seminiferous tubules and also guaranteeing homeostasis of the microenvironment for spermatogenesis for decades.…”

Clinical Pathway for Early Diagnosis of COVID-19: Updates from Experience to Evidence-Based Practice

“…The overall mortality rate is estimated to be 2.3% (1023 deaths among 44,762 confirmed cases of COVID-19), based on experience within China [67]. Compared with greater than 10% mortality of SARS-CoV [68] and 35% mortality of MERS-CoV [69], SARS-Cov-2 has a lower mortality rate but appears to be more contagious. The mortality rate may be even lower in the realworld setting once the infection has stabilized.…”

Male reproductive health and intergenerational metabolic responses from a small RNA perspective

“…Spermatogenesis is characterized by large changes in the energy requirement and the availability of substrates at each stage of sperm differentiation. Spermatogoniawhich lie close to the basal membranedepend on blood glucose to fuel glycolytic processes, whilst later stage spermatocytes and spermatidslocated deeper within the testisrequire lactate secreted by Sertoli cells [75,76]. In contrast, spermatozoa are more adaptable on which substratesfor example glucose, fructose and pyruvatethey use for their energy metabolism, which is believed to be an adaptation to the varying availability of substrates in the male and female reproductive tracts [77][78][79][80][81].…”