Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion–detorsion

Abstract

Context Testicular torsion–detorsion results in loss of germ cells and infertility. Pentoxifylline has been shown to prevent tissue damage. Aims To determine the effect of pentoxifylline on germ cell survival in torsion–detorsion induced apoptosis Methods Twenty male mice were divided into four groups of five animals each: Control, T1 (Torsion–detorsion + single dose 100 mg/kg Pentoxifylline/IP), T2 (Torsion–detorsion + daily 20 mg/kg pentoxifylline/IP for 2 weeks, and T/D (Torsion–detorsion only). 35th day after torsion–detorsion, the left testes of all the animals were harvested for histological and biochemical analysis. Key results Histomorpholoical analysis showed significant increase (P < 0.05) in seminiferous tubule diameter, Johnsen’s score and germ cells of Control and T1 compared to T2 and T/D, with no significant difference (P > 0.05) in testis weight, sertoli, leydig and myoid cells. Tunnel assay showed significant increase (P < 0.05) in apoptotic cells of T/D and T2 animals compared to Control and T1. RT-PCR analysis showed significant high (P < 0.01) mRNA expression of Bax gene in T/D compared to T1 and T2 and significant increase (P < 0.05) of Bcl2 in Control, T1, T2 compared to T/D. Nrf2-ARE transcripts revealed significant increase (P < 0.05) in Control and T1 compared to T2 and T/D. Western blot showed significantly increased (P < 0.05) caspase-3 in T/D compared to Control, T1 and T2. Conclusion Pentoxifylline promotes spermatogenesis and suppressed apoptosis induced by testicular torsion–detorsion. Implication Pentoxifylline could serve as adjunct therapy to surgery in the treatment of torsion–detorsion induced germ cell apoptosis.