Furuchi T, Masuko K, Nishimune Y, Obinata M, Matsui Y
Department of Cell Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Development. 1996 Jun;122(6):1703-9. doi: 10.1242/dev.122.6.1703.
During normal spermatogenesis, more than half of the germ cells undergo apoptosis, but the physiological significance and molecular mechanisms of this programmed cell death are largely unknown. Because Bcl-2 functions as a death repressor, we have investigated the effect of misexpressing Bcl-2 in spermatogonia in transgenic mice using the human bcl-2 cDNA under the control of the human polypeptide chain elongation factor 1alpha (EF-1alpha) promoter. In the 2-week-old transgenic testes, exogenous Bcl-2 was expressed in spermatogonia and massive accumulation of spermatogonia was observed in seminiferous tubules by 4 weeks. At this time, only a few spermatocytes were apparent, and the accumulated cells degenerated, leading to vacuolization in some seminiferous tubules by 7 weeks. In older transgenic mice, abnormal accumulation of spermatogonia and degeneration of these germ cells was still observed, but some seminiferous tubules in which the level of Bcl-2 expression was reduced recovered normal spermatogenesis. These observations indicate that spermatogonial apoptosis is part of the normal program of mammalian spermatogenesis and is regulated by a pathway affected by Bcl-2.
在正常精子发生过程中,超过半数的生殖细胞会经历凋亡,但其生理意义和这种程序性细胞死亡的分子机制仍大多未知。由于Bcl-2作为一种死亡抑制因子发挥作用,我们利用人多肽链延长因子1α(EF-1α)启动子控制下的人bcl-2 cDNA,研究了在转基因小鼠精原细胞中错误表达Bcl-2的影响。在2周龄的转基因睾丸中,外源性Bcl-2在精原细胞中表达,到4周时在生精小管中观察到精原细胞大量积累。此时,仅可见少数精母细胞,积累的细胞发生退化,到7周时导致一些生精小管出现空泡化。在年龄较大的转基因小鼠中,仍观察到精原细胞异常积累和这些生殖细胞退化,但一些Bcl-2表达水平降低的生精小管恢复了正常精子发生。这些观察结果表明,精原细胞凋亡是哺乳动物精子发生正常程序的一部分,并受Bcl-2影响的一条途径调控。