State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Cell Death Dis. 2017 Oct 26;8(10):e3142. doi: 10.1038/cddis.2017.555.
Spermatogenesis, which involves mitosis and meiosis of male germ cells, is a highly complicated and coordinately ordered process. Cyclin B1 (CCNB1), an important regulator in cell cycle machinery, is proved essential for mouse embryonic development. However, the role of CCNB1 in mammalian spermatogenesis remains unclear. Here we tested the requirement for CCNB1 using conditional knockout mice lacking CCNB1 in male germ cells. We found that ablation of CCNB1 in gonocytes and spermatogonia led to mouse sterile caused by the male germ cells' depletion. Gonocyte and spermatogonia without CCNB1 is unable to proliferate normally and apoptosis increased. Moreover, CCNB1 ablation in spermatogonia may promote their differentiation by downregulating Lin28a and upregulating let-7 miRNA. However, ablation of CCNB1 in premeiotic male germ cells did not have an effect on meiosis of spermatocytes and male fertility, suggesting that CCNB1 may be dispensable for meiosis of spermatocytes. Collectively, these results indicate that CCNB1 is critically required for the proliferation of gonocytes and spermatogonia but may be redundant in meiosis of spermatocytes in mouse spermatogenesis.
精子发生涉及雄性生殖细胞的有丝分裂和减数分裂,是一个高度复杂和协调有序的过程。细胞周期蛋白 B1(CCNB1)是细胞周期机制中的重要调节因子,被证明对小鼠胚胎发育至关重要。然而,CCNB1 在哺乳动物精子发生中的作用尚不清楚。在这里,我们使用缺乏雄性生殖细胞中 CCNB1 的条件敲除小鼠来测试 CCNB1 的需求。我们发现,生殖细胞和精原细胞中 CCNB1 的缺失导致雄性生殖细胞耗竭引起的小鼠不育。没有 CCNB1 的生殖细胞和精原细胞无法正常增殖,细胞凋亡增加。此外,精原细胞中 CCNB1 的缺失可能通过下调 Lin28a 和上调 let-7 miRNA 来促进它们的分化。然而,CCNB1 在减数分裂前期雄性生殖细胞中的缺失对精母细胞的减数分裂和雄性生育力没有影响,这表明 CCNB1 可能对精母细胞的减数分裂不是必需的。总之,这些结果表明 CCNB1 对于生殖细胞和精原细胞的增殖是至关重要的,但在小鼠精子发生的精母细胞减数分裂中可能是多余的。