GnRH Antagonist Improves Pubertal Cyclophosphamide-Induced Long-Term Testicular Injury in Adult Rats

Abstract

Background. Gonadal injury following chemotherapy is of increasing importance with the continuous improvement of survival rates. The protection of gonadotropin hormone antagonist (GnRHant) in long-term adult survivors of adolescent cancers and some autoimmune diseases has not yet been evaluated. Methods. The present study was aimed at longitudinally exploring whether the GnRHant could alleviate testicular damage induced by cyclophosphamide (CPA) in a rat model. Pubertal male rats were assigned to receive CPA with and without GnRHant. CPA was administrated at a single dose (100 mg/kg). GnRHant was started one hour prior to CPA injection and continued for four weeks (0.1 mg/kg, 3 times a week). Body and testes weights, testicular hormones, histological changes, and expression of androgen receptor (AR) in the testis were analyzed when rats matured into adulthood and completed a round of spermatogenesis. Results. Our results showed that body weight, histological injury, and AR expression in the testis were improved in the GnRHant + CPA group. However, testes weight and testicular hormones (anti-Müllerian hormone, inhibin B, and testosterone) did not markedly change. Conclusion. Our results indicate that the GnRHant administration before and after CPA in pubertal rats can protect long-term testicular injury induced by CPA via increased AR expression in the testes.