Stem cell factor/c-kit system in spermatogenesis
Stem cell factor/c-kit system in spermatogenesis
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DOI：
10.1093/humupd/5.5.535
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发表时间：
1999-09-01
影响因子：
13.3
通讯作者：
Benahmed, M
中科院分区：
文献类型：
--
作者：
Mauduit, C;Hamamah, S;Benahmed, M
目前诊断为特发性男性不育的绝大多数精子发生停滞的分子起源是男性不育的主要未解决的问题之一。在过去的几年中，几个家族的调节因子与基本上在动物模型中观察到的精子发生缺陷有关。这些因子中包括信号分子，特别是干细胞因子（SCF）/c-kit系统。SCF及其受体c-kit是阐明信号分子在精子发生的生理和病理中作用的一个恰当的例子。SCF/c-kit调节胚胎性腺发育过程中的原始生殖细胞迁移、增殖和凋亡，SCF/c-kit还调节成年动物精原细胞增殖。在突变小鼠中，SCF/c-kit基因表达异常，如基因缺失、点突变、选择性剪接缺陷等，导致不同类型的精子发生改变（例如，原始生殖细胞迁移的减少，精原细胞增殖的减少）。最近，SCF/c-kit基因表达的缺陷也已在人睾丸功能障碍中显示。事实上，SCF/c-kit表达的降低在少精子症/无精子症中已被证明与生殖细胞凋亡过程的增加有关。此外，c-kit似乎是一个很好的标记睾丸肿瘤，这篇综述报道了大量的数据，主要是在动物模型中获得的，这表明SCF/c-kit系统在精子发生中的重要作用，作为一个必然的结果，其潜在的参与精子发生缺陷。
One of the major unresolved questions with male infertility is the identification of the molecular origin of a great majority of the spermatogenetic arrests currently diagnosed as idiopathic male infertility During the past years, several families of regulating factors have been implicated in spermatogenesis defects observed essentially in animal models. Among these factors are signalling molecules, and particularly the stem cell factor (SCF)/c-kit system. The SCF and its receptor c-kit are an appropriate example to illustrate the role of signalling molecules in the physiology and pathology of spermatogenesis, The SCF/c-kit regulates primordial germ cell migration, proliferation and apoptosis during fetal gonadal development, The SCF/c-kit also regulates spermatogonia proliferation in the adult animal. Ln mutant mice, abnormalities of the SCF/c-kit gene expression, such as gene deletion, point mutation, alternative splicing defect, lead to different types of spermatogenesis alterations (e.g. decrease in primordial germ cell migration, decrease in spermatogonia proliferation), More recently defects in SCF/c-kit gene expression have also been shown in human testicular dysfunctions, Indeed, a reduction in SCF/c-kit expression has been evidenced in oligozoospermia/azoospermia associated with an increase in the germ cell apoptosis process. In addition, c-kit seems to be a good marker of seminoma testicular tumors, This review reports a large number of data-obtained essentially in animal models-that suggest an important role for the SCF/c-kit system in spermatogenesis and, as a corollary, its potential involvement in spermatogenic defects.