Secretome of human amniotic membrane stem cells promote recovery and testicular functions through modulating SIRT1/NRF2/TNF-α pathway in mice testicular torsion: An experimental study

Abstract

Background: Testicular ischemia/reperfusion injury, a significant result of testicular torsion, can lead to the risk of male infertility. Objective: The current study aimed to evaluate the effect of human amniotic membrane-derived mesenchymal stem cells (hAMSCs) secretome on testicular torsion/detorsion (T/D) in mice. Materials and Methods: All the experiments were performed in the Anatomy Department of Tehran University of Medical Sciences, Tehran, Iran, during the period of March 2023 to December 2023. 40 male NMRI mice (5–7 wk, 25–30 gr) were randomized into: 1) the sham group: mice received sham operations with no other interventions, 2) T/D group, 3) negative control group; torsion detorsion + intratesticular injection of Dulbecco’s Modified Eagle Medium/Nutrient Mixture F-12, and 4) the T/D group + hAMSCs secreted factors. Serum testosterone levels, hematoxylin and eosin staining, and sperm quality parameters were used to evaluate the therapeutic effects of hAMSCs secreted factors on the testicular structure and function. Tissue oxidative stress was measured by determining malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase-1. Nuclear factor erythroid 2-related factor 2, Kelch-like ECH-associated protein 1, NAD-dependent deacetylase sirtuin-1, tumor necrosis factor-alpha and tumor protein P53 mRNA expressions were assessed in testis via real-time polymerase chain reaction. Results: The results showed that hAMSCs secreted factors alleviated testicular T/D injury by attenuating oxidative stress, inflammatory response, and apoptosis via modulating the sirtuin-1/ nuclear factor erythroid 2-related factor 2 / tumor necrosis factor-alpha signaling pathway. Conclusion: hAMSCs secreted factors increased antioxidative, anti-inflammatory, and antiapoptotic properties which consequently increased testosterone levels, spermatogenesis, and sperm quality parameters.