Prmt5 is required for germ cell survival during spermatogenesis in mice

Yanbo Wang,Feng Han,Fei Gao,Xiuhong Cui,Yan Qin,Shilai Bao,Min Chen,Lianjun Zhang,Chunyi Liu,Tianxiang Zhu,Qiuling Li

doi:10.1038/srep11031

Abstract

During germ cell development, epigenetic modifications undergo extensive remodeling. Abnormal epigenetic modifications usually result in germ cell loss and reproductive defect. Prmt5 (Protein arginine methyltransferase 5) encodes a protein arginine methyltransferase which has been demonstrated to play important roles in germ cell development during embryonic stages. In the present study, we found that Prmt5 was also abundantly expressed in male germ cells after birth. Inactivation of this gene by crossing with Stra8-Cre transgenic mice resulted in germ cell loss during spermatogenesis. Further study revealed that the germ cell development was grossly normal before P10. However, most of the germ cells in Prmt5Δ/f; Stra8-Cre mice were blocked at meiotic stage. The expression of meiosis associated genes was reduced in Prmt5Δ/f; Stra8-Cre testes compared to control testes at P10. γH2AX was detected in sex body of control germ cells at P12, whereas multiple foci were observed in Prmt5-deficient germ cells. Further study revealed that H4R3me2s was virtually absent in germ cells after Prmt5 inactivation. The results of this study indicate that Prmt5 also plays important roles in germ cell development during spermatogenesis.

Highlights

Tumorigenesis[11,12]
The number of germ cells was dramatically reduced at P21 (Fig. 3F, black arrowheads) and only a few germ cells were observed in the seminiferous tubules in testes of adult Prmt5Δ/f; Stra8-Cre males (Fig. 3H, black arrowheads). These results indicate that the germ cells were gradually lost from P12 after Prmt[5] inactivation which causes the defect of spermatogenesis in Prmt5Δ/f; Stra8-Cre mice
DNA methylation plays critical roles in retrotransposon silencing and germ cell development, deletion of Dnmt3L in mouse model up-regulates the transcription of LINE and IAP retrotransposons in spermatogonia and spermatocytes

Summary

Introduction

Tumorigenesis[11,12]. Prmt[5] belongs to the PRMT family and is responsible for the formation of symmetric dimethylarginine (SMDA) in arginine-rich protein motifs[13]. It has been reported that Prmt[5] is essential for maintaining the pluripotency of mouse embryonic stem cells (ES). Prmt[5] is expressed in primordial germ cells (PGCs) and directs histone arginine methylation in mouse germ cells[16], recent studies found that inactivation of Prmt[5] in PGCs using Blimp1-Cre resulted in germ cells death before E12.517,18, suggesting that Prmt[5] plays essential roles in PGCs survival. We found that Prmt[5] was abundantly expressed in germ cells of adult testis, suggesting that histone methylation probably plays roles in spermatogenesis. The results of this study indicate that Prmt[5] is required for male germ cell survival during spermatogenesis

Methods

Results

Conclusion