Pentoxifylline Promotes Spermatogenesis Via Upregulation of the Nrf2-ARE Signalling Pathway in a Mouse Model of Germ-cell Apoptosis Induced by Testicular Torsion-detorsion

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 100mg/kg Pentoxifylline/IP), T2 (Torsion-detorsion+daily 20mg/kg pentoxifylline/IP for 2weeks, and T/D (Torsion-detorsion only). 35thday 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.