College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering & Technology, Northwest A & F University, Yangling, Shaanxi, China.
College of Veterinary Medicine, Shaanxi Center of Stem Cells Engineering & Technology, Northwest A & F University, Yangling, Shaanxi, China.
Biochim Biophys Acta Mol Cell Res. 2020 Oct;1867(10):118790. doi: 10.1016/j.bbamcr.2020.118790. Epub 2020 Jul 1.
Eukaryotic translation initiation factor 2 subunit 3 and structural gene Y-linked (Eif2s3y) gene, the gene encoding eIF2γ protein, is globally expressed in all tissues and plays important roles in regulating global and gene-specific mRNA translation initiation. It has been noticed that Eif2s3y plays crucial roles in spermatogenesis, however, the mechanism remains unclear. In the current study, transgenic Eif2s3y mice were generated to test our hypothesis that the Eif2s3y promotes the proliferation of spermatogonial stem cells (SSCs). Transgenic Eif2s3y mouse had enhanced SSCs proliferation rate when compared to WT mouse. Interesting, the testes from transgenic Eif2s3y mouse had increased Active-β-catenin protein expression and higher expression pattern of Wnt ligand Wnt6 when compared to testes from WT mouse. This study revealed novel roles of Eif2s3y in the activation Wnt6/β-catenin signal pathway in SSCs. Taken together, we identified Eif2s3y-Wnt6-β-catenin as a critical pathway in the regulation of spermatogenesis, which provides a platform for investigating the molecular mechanisms of male reproduction.
真核翻译起始因子 2 亚基 3 和结构基因 Y 连锁（Eif2s3y）基因，该基因编码 eIF2γ 蛋白，在所有组织中广泛表达，在调节全局和基因特异性 mRNA 翻译起始中发挥重要作用。人们注意到 Eif2s3y 在精子发生中起着至关重要的作用，然而，其机制尚不清楚。在本研究中，生成了转 Eif2s3y 基因小鼠，以验证我们的假设，即 Eif2s3y 促进精原干细胞（SSC）的增殖。与 WT 小鼠相比，转 Eif2s3y 基因小鼠的 SSC 增殖率更高。有趣的是，与 WT 小鼠的睾丸相比，转 Eif2s3y 基因小鼠的睾丸中 Active-β-catenin 蛋白表达增加，Wnt 配体 Wnt6 的表达模式更高。本研究揭示了 Eif2s3y 在 SSCs 中激活 Wnt6/β-catenin 信号通路中的新作用。总之，我们确定了 Eif2s3y-Wnt6-β-catenin 作为调节精子发生的关键途径，为研究男性生殖的分子机制提供了一个平台。
