GYY4137 a H2S donor, attenuates ipsilateral epididymis injury in experimentally varicocele-induced rats via activation of the PI3K/ Akt pathway

Objective(s): The current study was aimed to investigate the effect of morpholin-4-ium 4 methoxyphenyl (morpholino) phosphinodithioate (GYY4137) on ipsilateral epididymis injury in a rat model of experimental varicocele (VC). Materials and Methods: Sixty Wistar rats were randomly assigned to sham, sham plus GYY4137, VC and VC plus GYY4137 groups. Sperm quality parameters, including sperm count, motility and viability were evaluated after 4 weeks. Histological changes were measured by hematoxylin and eosin staining between the groups. The oxidative stress levels were estimated by determining epididymal superoxide dismutase (SOD) and malondialdehyde (MDA). The apoptosis status and the expression of phosphatidylinositol 3′-OH kinase (PI3K)/Akt were analyzed by immunohistochemical analysis, western blot and RT-qPCR. Results: VC resulted in the decrease of sperm parameters, significant histological damage and higher levels of oxidative stress and apoptosis. Compared to the VC group, GYY4137 markedly ameliorated these observed changes. In addition, treatment with GYY4137 obviously reduced the levels of caspase-3 and Bax and increased the levels of the phosphorylation of PI3K p85 and Akt. Conclusion: Our data demonstrated that GYY4137 may alleviate the sperm damage and epididymis injury in experimentally VC-induced rats by activation of the PI3K/Akt pathway.