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Published on: February 6, 2018
FTY720 inhibits germ cell apoptosis in testicular torsion/detorsion
Hung-Jen Shih1, Jiin-Cherng Yen2, Allen W Chiu3
1Division of Urology, Department of Surgery, Changhua Christian Hospital, Changhua, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
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.
Insights
FTY720 protects against testicular torsion/detorsion-induced germ cell apoptosis by engaging sphingosine-1-phosphate receptor 1 (S1PR1). This finding offers potential therapeutic strategies for preserving male fertility following testicular injury.
Area of Science:
- Reproductive Biology
- Cellular Biology
- Pharmacology
Background:
- Testicular torsion/detorsion (T/D) can cause germ cell apoptosis, potentially impairing spermatogenesis.
- FTY720, a sphingosine-1-phosphate receptor 1 (S1PR1) agonist, is known to inhibit apoptosis in ischemic stroke models.
- The study investigates FTY720's potential to reduce germ cell apoptosis in testicular T/D rat models.
Purpose of the Study:
- To determine if FTY720 can mitigate germ cell apoptosis induced by testicular torsion/detorsion in rats.
- To explore the role of sphingosine-1-phosphate receptor 1 (S1PR1) in the protective effects of FTY720.
Main Methods:
- Adult male Sprague-Dawley rats underwent testicular torsion/detorsion (T/D).
- Groups received T/D alone, T/D plus FTY720, or T/D plus FTY720 and an S1PR1 antagonist (VPC23019).
- Apoptosis and sperm counts were assessed 24 hours post-detorsion.
Main Results:
- FTY720 treatment significantly increased sperm counts and S1PR1 expression compared to T/D alone or T/D with antagonist.
- Apoptotic cell markers (TUNEL, cleaved caspase-3) were significantly reduced in the FTY720-treated group.
- Apoptotic signals were predominantly observed in germ cells.
Conclusions:
- FTY720 effectively mitigates germ cell apoptosis caused by testicular torsion/detorsion.
- The protective mechanism of FTY720 appears to involve the sphingosine-1-phosphate receptor 1 (S1PR1).
- These findings suggest FTY720 as a potential therapeutic agent for testicular torsion/detorsion injuries.
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