Protein Arginine Methyltransferase 6 Involved in Germ Cell Viability during Spermatogenesis and Down-Regulated by the Androgen Receptor.

Manling Luo,Qian Ma,Yuchi Li,Yaoting Gui,Jianbo Chen,Huan Guo,Yanli Gu,Shouren Lin,Zhimao Jiang

doi:10.3390/ijms161226186

Abstract

Androgens and the androgen receptor (AR) are of great importance to spermatogenesis and male fertility. AR knockout (ARKO) mice display a complete insensitivity to androgens and male infertility; however, the exact molecular mechanism for this effect remains unclear. In this study, we found that the expression levels of Prmt6 mRNA and protein were significantly up-regulated in the testes of ARKO mice compared to wild type (WT) mice. PRMT6 was principally localized to the nucleus of spermatogonia and spermatocytes by immunofluorescence staining. Furthermore, luciferase assay data showed that AR together with testosterone treatment suppressed Prmt6 transcription via binding to the androgen-responsive element (ARE) of the Prmt6 promoter. Moreover, knockdown of Prmt6 suppressed germ cells migration and promoted apoptosis. In addition, both of these cellular activities could not be enhanced by testosterone treatment. Taken together, these data indicate that PRMT6, which was down-regulated by AR and influenced cell migration and apoptosis of germ cells, could play a potentially important role in spermatogenesis.

Highlights

Androgens are critical steroid hormones that are responsible for the expression of the male phenotype, the accomplishment of sexual maturation, the maintenance of spermatogenesis as well as male reproductive function and behavior [1]
Prmt6 (Protein Arginine Methyltransferase 6) mRNA and protein arginine methyltransferase 6 (PRMT6) Protein Expression Were Increased in the Testes of AR knockout (ARKO) (Androgen Receptor Knockout) Mice
The results showed that the expression of Prmt6 mRNA and PRMT6 protein were increased in ARKO mice, we speculate that PRMT6 was probably regulated by androgen receptor (AR)

Summary

Introduction

Androgens are critical steroid hormones that are responsible for the expression of the male phenotype, the accomplishment of sexual maturation, the maintenance of spermatogenesis as well as male reproductive function and behavior [1]. AR belongs to the nuclear receptor super family, mediates the biological action of androgens and regulates the expression of a number of androgen-responsive genes [1,3,4]. To search for the AR-regulated genes that are involved in spermatogenesis, transcriptional profiling studies of an AR knockout (ARKO) mouse model have been used. Using this mouse model, researchers have identified many candidate target genes of AR, such as Rhox5 [6], Tubb3 [7], and c-myc [8], but only Rhox has been characterized as a target of AR. Additional genes require further study to determine whether they are regulated by AR and are physiologically relevant to spermatogenesis

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Conclusion