In the current study, we have demonstrated for the first time in vivo, using a conditional Hnrnpu knockout mouse strain, that hnRNPU plays a central role in regulating Sertoli cell function and neonatal testicular development, and that deactivation of hnRNPU in Sertoli cells leads to severe testicular atrophy and male infertility. This evidence concerns the gene HNRNPU and male infertility.