Pentoxifylline promotes spermatogenesis via upregulation of the Nrf2-ARE signalling pathway in a mouse model of germ-cell apoptosis induced by testicular torsion–detorsion
Omotosho Dhulqarnain Akanji
A , Golamreza Hassanzadeh B , Mehrnoush Malekzadeh C , Nasrin Khanmohammadi B , Maryam Khanezad C , Ghazaleh Sadeghiani B and Tayebeh Rastegar B D *
+ Author Affiliations
- Author Affiliations
A Department of Anatomy, Faculty of Basic Medical Sciences, Olabisi Onabanjo University, Sagamu, Ogun State, Nigeria.
B Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
C Department of Anatomy, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
D Burns and Regenerative Medicine Research Center, Guilan University of Medical Sciences, Rasht, Iran.
Reproduction, Fertility and Development 35(7) 423-432 https://doi.org/10.1071/RD22168
Published online: 17 April 2023
© 2023 The Author(s) (or their employer(s)). Published by CSIRO Publishing
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.
Keywords: apoptosis, detorsion, germ cells, infertility, pentoxifylline, spermatocytes, spermatogenesis, testes, torsion.
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