Chronic prostatitis/chronic pelvic pain syndrome impairs erectile function by inducing apoptosis in a rat model of experimental autoimmune prostatitis.

Abstract

Over the years, numerous epidemiological studies have shown that chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) promotes erectile dysfunction. Nonetheless, the precise underlying mechanism remains to be fully clarified. The objective of this research was to identify crucial signaling pathways responsible for CP/CPPS-induced erectile dysfunction. Thirty 8-week-old male Sprague‒Dawley rats were randomly assigned to either the CP/CPPS model group or the control group. The CP/CPPS rat model was established through subcutaneous injection of a combination of rat prostate protein and Freund's adjuvant. Penile erectile function assessment was conducted 45 days after immunization through electrical stimulation of the cavernous nerve. RNA sequencing of the corpus cavernosum of the penis was then performed using the Kyoto Encyclopedia of Genes and Genomes and protein‒protein interaction network analysis. Western blotting was performed on the cavernous tissue. Cell apoptosis assays, cell counting kit-8 assays, cell cloning assays, and Western blotting were conducted on rat endothelial cells. Erectile function was significantly lower in the CP/CPPS model group than in the control group (p < 0.001). Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that differentially expressed genes were predominantly enriched in the apoptosis pathway. Moreover, an increase in apoptosis in the rat corpus cavernosum, along with a decrease in the protein expression of CD31 (p = 0.0089) and eNOS (p = 0.0069) following CP/CPPS induction, was observed. In a protein‒protein interaction network, Pitx2 was recognized as a central gene. The role of Pitx2 in regulating apoptosis was demonstrated in experiments using rat endothelial cell lines, and it was found to be regulated by the Wnt/β-catenin pathway. This study highlights the occurrence of cavernous endothelial cell apoptosis in CP/CPPS-induced erectile dysfunction, and the potential mechanism of apoptosis may involve inhibition of the Wnt/β-catenin/Pitx2 pathway.