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，编码eIF2γ蛋白的基因，在所有组织中普遍表达，在调节整体和基因特异性mRNA翻译起始中起重要作用。已经注意到，Eif2s3y在精子发生中起关键作用，但是其机制仍不清楚。在当前的研究中，产生了转基因Eif2s3y小鼠以检验我们的假设，即Eif2s3y促进精原干细胞（SSCs）的增殖。与WT小鼠相比，转基因Eif2s3y小鼠具有增强的SSCs增殖速率。有趣的是，来自转基因Eif2s3y的睾丸与来自WT小鼠的睾丸相比，小鼠具有增加的Active-β-catenin蛋白表达和较高的Wnt配体Wnt6表达模式。这项研究揭示了Eif2s3y在SSCs激活Wnt6 /β-catenin信号通路中的新作用。综上所述，我们确定Eif2s3y - Wnt6 - β -catenin是调控精子发生的关键途径，这为研究男性生殖的分子机制提供了平台。