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首页> 外文期刊>Cell Division >Impaired germ cell development due to compromised cell cycle progression in Skp2-deficient mice
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Impaired germ cell development due to compromised cell cycle progression in Skp2-deficient mice

机译：Skp2缺陷小鼠的细胞周期进程受损，导致生殖细胞发育受损

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Background The gonads are responsible for the production of germ cells through both mitosis and meiosis. Skp2 is the receptor subunit of an SCF-type ubiquitin ligase and is a major regulator of the progression of cells into S phase of the cell cycle, which it promotes by mediating the ubiquitin-dependent degradation of p27, an inhibitor of cell proliferation. However, the role of the Skp2-p27 pathway in germ cell development remains elusive. Results We now show that disruption of Skp2 in mice results in a marked impairment in the fertility of males, with the phenotypes resembling Sertoli cell-only syndrome in men. Testes of Skp2-/- mice manifested pronounced germ cell hypoplasia accompanied by massive apoptosis in spermatogenic cells. Flow cytometry revealed an increased prevalence of polyploidy in spermatozoa, suggesting that the aneuploidy of these cells is responsible for the induction of apoptosis. Disruption of the p27 gene of Skp2-/- mice restored germ cell development, indicating that the testicular hypoplasia of Skp2-/- animals is attributable to the antiproliferative effect of p27 accumulation. Conclusion Our results thus suggest that compromised cell cycle progression caused by the accumulation of p27 results in aneuploidy and the induction of apoptosis in gonadal cells of Skp2-/- mice. The consequent reduction in the number of mature gametes accounts for the decreased fertility of these animals. These findings reinforce the importance of the Skp2-p27 pathway in cell cycle regulation and in germ cell development.
机译：背景：性腺负责通过有丝分裂和减数分裂产生生殖细胞。 Skp2是SCF型泛素连接酶的受体亚基，是细胞进入细胞周期S期的主要调节因子，它通过介导泛素依赖性降解p27（一种细胞增殖抑制剂）来促进。但是，Skp2-p27途径在生殖细胞发育中的作用仍然难以捉摸。结果我们现在表明，破坏小鼠的Skp2会导致雄性的生育能力明显受损，其表型类似于男性的Sertoli细胞综合征。 Skp2 -// 小鼠的睾丸表现出明显的生殖细胞发育不全，伴生精细胞大量凋亡。流式细胞仪显示精子中多倍体的发生率增加，表明这些细胞的非整倍体是诱导凋亡的原因。 Skp2 -// 小鼠p27基因的破坏恢复了生殖细胞的发育，表明Skp2 -/-动物的睾丸发育不全归因于p27积累的抗增殖作用。结论因此，我们的结果表明，p27积累引起的细胞周期进程受损导致非整倍性和Skp2 -//-小鼠性腺细胞的凋亡诱导。因此，成熟配子数量的减少说明了这些动物的生育力下降。这些发现加强了Skp2-p27途径在细胞周期调控和生殖细胞发育中的重要性。

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