Related Experiment Video
Updated: May 24, 2026
Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
Published on: November 8, 2015
Sirolimus-associated testicular toxicity: detrimental but reversible
Jordi Rovira1, Fritz Diekmann, María José Ramírez-Bajo
1Laboratori Experimental de Nefrologia I Trasplantament, Department of Nephrology and Renal Transplantation, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain. jrovira1@clinic.ub.es
Background:
Mammalian target of rapamycin (mTOR) inhibition has been associated with gonadal dysfunction. The aim of this study was to characterize the effect of sirolimus (SRL) on male gonadal function in an experimental model.
Methods:
Male Wistar rats were treated with intraperitoneal administration of vehicle or SRL. Vehicle group was treated for 12 weeks. Rats treated with SRL were killed at 4, 8, and 12 weeks. A group of rats was treated with SRL for 4 weeks and then observed during 8 weeks to analyze the possible reversibility of the effect of mTOR inhibition. Body and testicular weight, testosterone, follicle-stimulating hormone level, and luteinizing hormone level were measured and testicular histology was analyzed including proliferation and apoptosis analysis.
Results:
Testicular weight was significantly lower in all SRL groups. After SRL withdrawal testicular weight had partially recovered. The expression of steroidogenic acute regulatory protein decreased during SRL treatment, which could explain the reduction of testosterone levels, because steroidogenic acute regulatory protein is crucial for testosterone synthesis. Spermatogenesis was blocked on the spermatogonial level by SRL treatment. Withdrawal of SRL treatment led to complete recovery.
Conclusions:
mTOR inhibition in healthy animals produces sexual hormone dysfunction, seminiferous tubule dystrophy and spermatogenesis blockade. Furthermore, the spermatogenesis blockade produced by SRL is reversible.
Insights
Sirolimus (SRL), an mTOR inhibitor, impairs male reproductive function by reducing testosterone and blocking spermatogenesis. However, these effects are reversible after SRL withdrawal.
Area of Science:
- Reproductive Endocrinology
- Pharmacology
Background:
- Mammalian target of rapamycin (mTOR) inhibition is linked to gonadal dysfunction.
- Investigating the specific impact of sirolimus (SRL) on male reproductive health is crucial.
Purpose of the Study:
- To evaluate the effects of mTOR inhibition by sirolimus on male gonadal function in an experimental rat model.
- To assess the reversibility of sirolimus-induced reproductive changes.
Main Methods:
- Wistar rats received vehicle or sirolimus (SRL) via intraperitoneal injection.
- Measurements included body/testicular weight, hormone levels (testosterone, FSH, LH), and testicular histology with proliferation/apoptosis analysis.
- Reversibility was assessed after a 4-week SRL treatment followed by an 8-week observation period.
Main Results:
- Sirolimus significantly reduced testicular weight and testosterone levels, linked to decreased steroidogenic acute regulatory protein expression.
- Spermatogenesis was blocked at the spermatogonial level in SRL-treated rats.
- Testicular weight partially recovered post-SRL withdrawal, and spermatogenesis fully recovered.
Conclusions:
- mTOR inhibition with sirolimus causes sexual hormone dysfunction, testicular damage, and spermatogenesis blockade in healthy male rats.
- The spermatogenesis blockade induced by sirolimus is reversible upon drug withdrawal.
