The REGγ-Proteasome Regulates Spermatogenesis Partially by P53-PLZF Signaling

Abstract

Summary: Development of spermatogonia and spermatocytes are the critical steps of spermatogenesis, impacting on male fertility. Investigation of the related regulators benefits the understanding of male reproduction. The proteasome system has been reported to regulate spermatogenesis, but the mechanisms and key contributing factors in vivo are poorly explored. Here we found that ablation of REGγ, a proteasome activator, resulted in male subfertility. Analysis of the mouse testes after birth showed there was a decreased number of PLZF+ spermatogonia and spermatocytes. Molecular analysis found that REGγ loss significantly increased the abundance of p53 protein in the testis, and directly repressed PLZF transcription in cell lines. Of note, allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. In summary, our results identify REGγ-p53-PLZF to be a critical pathway that regulates spermatogenesis and establishes a new molecular link between the proteasome system and male reproduction. : In this article, Lei Li and colleagues show that ablation of REGγ, a proteasome activator, resulted in male subfertility, partially because of a decreased number of PLZF+ spermatogonia and spermatocytes. Mechanistically, REGγ loss significantly increased the abundance of p53 protein, and transcriptionally represses PLZF expression. Allelic p53 haplodeficiency partially rescued the defects in spermatogenesis observed in REGγ-deficient mice. Keywords: REGγ, PLZF, p53, spermatogonial stem cells, mouse reproduction