An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis

An early and massive wave of germinal cell apoptosis is required for the development of functional spermatogenesis
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DOI:
10.1093/emboj/16.9.2262
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发表时间:
1997-05-01
期刊:
影响因子:
11.4
通讯作者:
Vassalli, P
Vassalli, P
中科院分区:
生物学1区
文献类型:
--
作者:
Rodriguez, I;Ody, C;Vassalli, P

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在雄性生殖细胞中表达高水平BclxL或Bcl2蛋白的转基因小鼠显示出伴随不育的高度异常的成年精子发生。这似乎是由于防止了睾丸中早期和大量的细胞凋亡,这发生在第一轮精子发生期间的生殖细胞中。相反,在成年转基因小鼠中,发生在正常成年睾丸中的精原细胞之间的零星凋亡并没有被阻止。睾丸中的生理性早期凋亡波在时间和定位上与促凋亡蛋白Bax的暂时高表达一致,Bax在性成熟时消失。BclxL和Bax蛋白(Bcl 2在正常小鼠睾丸中显然不表达)的细胞内平衡(可能是睾丸控制的)在这种早期凋亡波中发挥的关键作用,通过在Bax基因缺陷的小鼠中发生类似的睾丸综合征来显示。凋亡波似乎是正常成熟精子发生发展所必需的,可能是因为它在某些生殖细胞阶段和支持细胞之间保持了一个临界的细胞数量比,支持细胞的正常功能和分化涉及一个复杂的通讯网络。
Transgenic mice expressing high levels of the BclxL or Bcl2 proteins in the male germinal cells show a highly abnormal adult spermatogenesis accompanied by sterility. This appears to result from the prevention of an early and massive wave of apoptosis in the testis, which occurs among germinal cells during the first round of spermatogenesis. In contrast, sporadic apoptosis among spermatogonia, which occurs in normal adult testis, is not prevented in adult transgenic mice. The physiological early apoptotic wave in the testis is coincident, in timing and localization, with a temporary high expression of the apoptosis-promoting protein Bax, which disappears at sexual maturity. The critical role played by the intracellular balance, probably hormonally controlled, of the BclxL and Bax proteins (Bcl2 is apparently not expressed in normal mouse testis) in this early apoptotic wave is shown by the occurrence of a comparable testicular syndrome in mice defective in the bax gene. The apoptotic wave appears necessary for normal mature spermatogenesis to develop, probably because it maintains a critical cell number ratio between some germinal cell stages and Sertoli cells, whose normal functions and differentiation involve an elaborate network of communication.