FTY720 inhibits germ cell apoptosis in testicular torsion/detorsion

J Surg Res. 2016 May 1;202(1):155-64. doi: 10.1016/j.jss.2015.12.035. Epub 2015 Dec 30.

Abstract

Background: Testicular torsion/detorsion (T/D) can induce germ cells apoptosis, which may lead to impairment of spermatogenesis. FTY720, an agonist of the sphingosine-1-phosphate receptor 1 (S1PR1), inhibits apoptosis in ischemic stroke. We examined whether FTY720 could mitigate germ cell apoptosis in testicular T/D rats.

Materials and methods: Adult male Sprague-Dawley rats were allocated to receive testicular T/D (the T/D group), T/D plus FTY720 (the T/D-FTY group), or T/D plus FTY720 plus the potent S1PR1 antagonist VPC23019 (the T/D-FTY-VPC group; n = 6 in each group). Sham control groups were run simultaneously. At 24 h after detorsion, rats were euthanized.

Results: Our data revealed that, in the ipsilateral twisted testes, sperm counts and expression of the S1PR1 of the T/D and the T/D-FTY-VPC groups were significantly lower than those of the T/D-FTY group (all P < 0.001). In contrast, signals of apoptotic cells stained by terminal deoxynucleotidyl transferase dUTP nick end labeling and the proapoptotic protein cleaved caspase-3 of the T/D, and the T/D-FTY-VPC groups were significantly stronger than those of the T/D-FTY group. Moreover, the terminal deoxynucleotidyl transferase dUTP nick end labeling signals mainly localized to germ cells.

Conclusions: FTY720 could mitigate testicular T/D-induced germ cell apoptosis, and the mechanisms may involve the S1PR1.

Keywords: Apoptosis; Germ cells; Ischemic reperfusion; Testis; Torsion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Fingolimod Hydrochloride / pharmacology*
  • Fingolimod Hydrochloride / therapeutic use
  • In Situ Nick-End Labeling
  • Male
  • Protective Agents / pharmacology*
  • Protective Agents / therapeutic use
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Spermatic Cord Torsion / drug therapy*
  • Spermatic Cord Torsion / pathology
  • Spermatic Cord Torsion / physiopathology
  • Spermatic Cord Torsion / therapy
  • Spermatozoa / drug effects*
  • Spermatozoa / pathology
  • Spermatozoa / physiology
  • Treatment Outcome

Substances

  • Protective Agents
  • Fingolimod Hydrochloride