Eif2s3y regulates the proliferation of spermatogonial stem cells via Wnt6/<beta>-catenin signaling pathway

Biochim Biophys Acta Mol Cell Res. 2020 Oct;1867(10):118790. doi: 10.1016/j.bbamcr.2020.118790. Epub 2020 Jul 1.

Abstract

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.

Keywords: Eif2s3y; Mouse; Proliferation; Spermatogonial stem cells; Wnt6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation
  • Male
  • Mice, Transgenic
  • Models, Biological
  • Proto-Oncogene Proteins / metabolism*
  • Spermatogonia / cytology*
  • Stem Cells / cytology*
  • Transcription Factors / metabolism*
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway*

Substances

  • Eif2s3y protein, mouse
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Wnt Proteins
  • Wnt6 protein, mouse