Premeiotic germ cell defect in seminiferous tubules of Atm-null testis.
Premeiotic germ cell defect in seminiferous tubules of Atm-null testis.
复制标题
DOI：
10.1016/j.bbrc.2006.10.145
复制
发表时间：
2006-12
影响因子：
3.1
通讯作者：
K. Takubo;A. Hirao;M. Ohmura;Masaki Azuma;F. Arai;Go Nagamatsu;T. Suda
中科院分区：
文献类型：
--
作者：
K. Takubo;A. Hirao;M. Ohmura;Masaki Azuma;F. Arai;Go Nagamatsu;T. Suda
终身精子发生是由协调的连续过程维持的，包括干细胞的自我更新、精原细胞的增殖、减数分裂和精子发生。研究表明，共济失调毛细血管扩张突变（ATM）是生精小管减数分裂所必需的。在这里，我们表明，除了其在减数分裂中的作用，ATM在减数分裂前生殖细胞的维护中具有举足轻重的作用。ATM在减数分裂前精原细胞中被激活，ATM缺失的睾丸显示进行性变性。在Atm-null睾丸细胞中，不同于Atm-null小鼠的骨髓细胞，活性氧介导的p16 Ink 4a活化不发生在Atm-null减数分裂前生殖细胞中，这表明骨髓缺陷涉及不同的信号通路。尽管Atm-null骨髓经历p16 Ink 4a介导的细胞衰老程序，但Atm-null减数分裂前生殖细胞表现出细胞周期停滞和减数分裂前生殖细胞的凋亡消除，这与p16 Ink 4a介导的衰老不同。
Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16Ink4aactivation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16Ink4a-mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16Ink4a-mediated senescence.