Inactivation of the Celf1 gene that encodes an RNA-binding protein delays the first wave of spermatogenesis in mice

PLoS One. 2012;7(10):e46337. doi: 10.1371/journal.pone.0046337. Epub 2012 Oct 2.

Abstract

Background: The first wave of spermatogenesis in mammals is characterized by a sequential and synchronous appearance of germ cells in the prepubertal testis. Post-transcriptional controls of gene expression play important roles in this process but the molecular actors that underlie them are poorly known.

Methodology/principal findings: We evaluated the requirement for the RNA-binding protein CELF1 during the first wave of spermatogenesis in mice. Mice inactivated for Celf1 gene were not viable on pure genetic backgrounds. On a mixed background, we observed by histology and gene profiling by RT-qPCR that the testes of inactivated prepubertal mice were characterized by several features. (i) Spermiogenesis (differentiation of post-meiotic cells) was blocked in a subset of prepubertal inactivated mice. (ii) The appearance of the different stages of germ cell development was delayed by several days. (iii) The expression of markers of Leydig cells functions was similarly delayed.

Conclusions/significance: Celf1 disruption is responsible for a blockage of spermiogenesis both in adults and in prepubertal males. Hence, the spermiogenesis defects found in Celf1-inactivated adults appear from the first wave of spermiogenesis. The disruption of Celf1 gene is also responsible for a fully penetrant delayed first wave of spermatogenesis, and a delay of steroidogenesis may be the cause for the delay of germ cells differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CELF1 Protein
  • Gene Expression Profiling
  • Gene Silencing*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Polymerase Chain Reaction
  • RNA-Binding Proteins / genetics*
  • Spermatogenesis / genetics*

Substances

  • CELF1 Protein
  • CELF1 protein, mouse
  • RNA-Binding Proteins

Grants and funding

This work was supported by grants from the Association pour la Recherche Contre le Cancer [ARC4003 to LP, http://www.arc-cancer.net/] and Agence Nationale de la Recherche [ANR-07-JCJC-0097-01 to LP, http://www.agence-nationale-recherche.fr/]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.