PRPS2 Expression Correlates with Sertoli-Cell Only Syndrome and Inhibits the Apoptosis of TM4 Sertoli Cells

J Urol. 2015 Nov;194(5):1491-7. doi: 10.1016/j.juro.2015.04.116. Epub 2015 May 22.

Abstract

Purpose: Sertoli-cell only syndrome is one of the reasons for male infertility but its pathogenesis remains unclear. PRPS2, a subset of PRS, is reported to be a potential protein associated with Sertoli-cell only syndrome. In this study we further investigated the correlation between PRPS2 and Sertoli-cell only syndrome, and evaluated the effect of PRPS2 expression on apoptosis of TM4 Sertoli cells.

Materials and methods: PRPS2 expression was detected in patients with Sertoli-cell only syndrome and normal spermatogenesis, and in Sertoli-cell only syndrome mouse models by immunohistochemistry, quantitative reverse transcription-polymerase chain reaction and Western blot. PRPS2 expression in TM4 Sertoli cells was then down-regulated and up-regulated by lentivirus vectors. The effect of PRPS2 expression on cell apoptosis and cell cycle transition was evaluated by flow cytometry.

Results: PRPS2 expression in patients with Sertoli-cell only syndrome was significantly greater than in those with normal spermatogenesis. A significant increase in PRPS2 expression was observed in Sertoli-cell only syndrome mouse models. PRPS2 over expression significantly inhibited cell apoptosis and promoted cell cycle transition in TM4 Sertoli cells. However, PRPS2 down-regulation showed a reverse effect. Moreover, results revealed that PRPS2 over expression inhibited cell apoptosis via the p53/Bcl-2/caspase-9/caspase-3/caspase-6/caspase-7 signaling pathway.

Conclusions: PRPS2 expression correlates with Sertoli-cell only syndrome and inhibits the apoptosis of TM4 Sertoli cells via the p53/Bcl-2/caspases signaling pathway.

Keywords: Sertoli cell-only syndrome; infertility; male; p53; phosphoribosylpyrophosphate synthetase superactivity; testis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Apoptosis / genetics*
  • Blotting, Western
  • Cells, Cultured
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Middle Aged
  • RNA / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribose-Phosphate Pyrophosphokinase / biosynthesis
  • Ribose-Phosphate Pyrophosphokinase / genetics*
  • Sertoli Cell-Only Syndrome / genetics*
  • Sertoli Cell-Only Syndrome / metabolism
  • Sertoli Cell-Only Syndrome / pathology
  • Sertoli Cells / metabolism
  • Sertoli Cells / pathology*
  • Young Adult

Substances

  • RNA
  • PRPS2 protein, human
  • Ribose-Phosphate Pyrophosphokinase