Said Tamer M, Paasch Uwe, Glander Hans-Juergen, Agarwal Ashok
Center for Advanced Research in Human Reproduction, Infertility, and Sexual Function, Glickman Urological Institute and Department of Obstetrics & Gynecology, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk A19.1, Cleveland, OH 44195, USA.
Hum Reprod Update. 2004 Jan-Feb;10(1):39-51. doi: 10.1093/humupd/dmh003.
Apoptosis is characterized by a variety of changes resulting in the recognition and phagocytosis of apoptotic cells. Caspases (cysteinyl aspartate-specific proteinases) play a central role in the regulation of apoptosis in the human seminiferous epithelium. They are expressed as inactive proenzymes and participate in a cascade triggered in response to pro-apoptotic signals. To date, 14 caspases have been implicated in the human apoptotic pathway cascade. Among these, caspase-3 is considered to be a major executioner protease. Since apoptosis is a universal suicide system in almost all cells, a close control via molecular, endocrine and physical factors establishes homeostasis of cell growth and death. The proper regulation of the caspase cascade plays an important role in sperm differentiation and testicular maturity. However, caspases have been implicated in the pathogenesis of multiple andrological pathologies such as impaired spermatogenesis, decreased sperm motility and increased levels of sperm DNA fragmentation, testicular torsion, varicocele and immunological infertility. Future research may provide a better understanding of the regulation of caspases, which may help us to manipulate the apoptotic machinery for therapeutic benefits. In this review, we summarize the consequences of caspase activation, aiming to clarify their role in the pathogenesis of male infertility.
细胞凋亡的特征是发生多种变化，最终导致凋亡细胞被识别并被吞噬。半胱天冬酶（天冬氨酸特异性半胱氨酸蛋白酶）在人类生精上皮细胞凋亡的调控中起核心作用。它们以无活性的酶原形式表达，并参与响应促凋亡信号而触发的级联反应。迄今为止，已有14种半胱天冬酶参与人类凋亡途径级联反应。其中，半胱天冬酶-3被认为是主要的执行蛋白酶。由于细胞凋亡几乎是所有细胞中普遍存在的自杀系统，通过分子、内分泌和物理因素进行密切调控可建立细胞生长与死亡的稳态。半胱天冬酶级联反应的恰当调控在精子分化和睾丸成熟过程中发挥重要作用。然而，半胱天冬酶已被证实与多种男性生殖系统疾病的发病机制有关，如精子发生受损、精子活力下降、精子DNA片段化水平升高、睾丸扭转、精索静脉曲张和免疫性不育。未来的研究可能会让我们更好地理解半胱天冬酶的调控机制，这或许有助于我们操控凋亡机制以获得治疗益处。在本综述中，我们总结了半胱天冬酶激活的后果，旨在阐明它们在男性不育发病机制中的作用。
