Abstract
Using a surgically induced varicocele rat model, we show here strong evidence that the misfolded/unfolded protein response that is part of the stress response of the endoplasmic reticulum (ER) is activated in the varicocele testis (VCL), leading to the induction of apoptosis. To support this hypothesis, it is observed that the spliced variant of the X-box protein 1 (XBP1s), resulting from the activation of the inositol-requiring enzyme 1 (IRE1) membrane sensor, is significantly more represented in VCL testicular extracts. The activation of the IRE1/XBP1s pathway is also supported by the observation that the VCL testes show an increase phosphorylation of the c-Jun-kinase (JNK) known to be one intermediate of this pathway and an increased level of caspase-3, the terminal apoptotic effector, partly explaining the apoptotic status of the VCL testis.
Highlights
Varicocele (VCL) is a large varicose dilatation of the spermatic cord veins located in the bursa above and around each testicle [1]
To test whether VCL testis could be concerned by UPR/endoplasmic reticulum (ER) stress mechanisms, we used our expertise in VCL-induced rat models [24,25,26,27,28]
After verifying that our VCL-induced animals had all the classical characteristics expected in terms of testicular damage and sperm distorted parameters [28, 38,39,40], we focused our research on marker characteristics of UPR/ER stress pathways
Summary
Varicocele (VCL) is a large varicose dilatation of the spermatic cord veins located in the bursa above and around each testicle [1]. With approximately 15% of the adult male population affected, varicocele is a relatively common disease that can occur at any age. It is clear that higher scrotal temperature, inflammation, hypoxia, nutrient deprivation, oxidative stress, and increased apoptosis are characteristics of the varicocele testis, the full spectrum of the dysfunctional organ is not yet well defined [4]. In this complex picture, the increased generation of reactive oxygen species (ROS)
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