title: FTY720 inhibits germ cell apoptosis in testicular torsion/detorsion.
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.
  
  
  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.
authors.affiliation: Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hung-Jen
authors.initials: HJ
authors.lastname: Shih
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Jiin-Cherng
authors.initials: JC
authors.lastname: Yen
authors.affiliation: School of Medicine, National Yang-Ming University, Taipei, Taiwan; Taipei City Hospital, Taipei, Taiwan.
authors.forename: Allen W
authors.initials: AW
authors.lastname: Chiu
authors.affiliation: Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Medical College, Taipei, Taiwan.
authors.forename: Yung-Chiong
authors.initials: YC
authors.lastname: Chow
authors.affiliation: Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wynn H T
authors.initials: WH
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Taipei Tzu Chi Hospital, Taipei, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan. Electronic address: huangcj1112@gmail.com.
authors.forename: Chun-Jen
authors.initials: CJ
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D008297:Male; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013086:Spermatic Cord Torsion / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D013094:Spermatozoa / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D016896:Treatment Outcome
chemical_list: D020011:Protective Agents; D000068876:Fingolimod Hydrochloride
keywords: Apoptosis; Germ cells; Ischemic reperfusion; Testis; Torsion