Inactivation of the Celf1 Gene that Encodes an RNA-Binding Protein Delays the First Wave of Spermatogenesis in Mice

Marie Cibois,Gaella Boulanger,Yann Audic,Luc Paillard,Carole Gautier-Courteille

doi:10.1371/journal.pone.0046337

Abstract

BackgroundThe 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 findingsWe 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.

Highlights

Mammalian spermatogenesis is a complex process that can be divided into three stages
We found that the inactivation of Celf1 hampers spermiogenesis in prepubertal animals like is adults, and delays the first wave of spermatogenesis at both the germ cells and Leydig cells levels
We have previously shown that the sterility phenotype of Celf1inactivated mice (Celf1tm1Cba/tm1Cba, hereafter Celf12/2 or 2/2) was not fully penetrant

Summary

Introduction

Mammalian spermatogenesis is a complex process that can be divided into three stages. The post-meiotic phase, or spermiogenesis, is characterized by deep morphological and structural modifications of germ cells that transform round spermatids into elongated spermatids and spermatozoa [2]. This complex differentiation process requires stage-specific expression of several gene products, and relies on tightly controlled gene expression. A prerequisite to understand these regulations is to characterize the stage-specific transcriptomes of germ cells. This was achieved by microarray analysis starting from enriched germ cell populations [3], and starting from different ages of prepubertal testes. The first wave of spermatogenesis is blocked at the round spermatid stage in about half of the 2/2 mice.

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