Autoimmune prostatitis in rats drives sexual dysfunction via neuroinflammation, altered neurochemicals, and `cGMP-PKG`/`MAPK` pathway dysregulation.

Male sexual dysfunction is a common and debilitating symptom of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), yet the precise central mechanisms linking these conditions remain poorly understood. Current understanding often focuses on peripheral inflammation, overlooking potential neuroimmune interactions. This knowledge gap hinders the development of targeted therapies. This study aimed to bridge this gap by using a multi-omics approach to uncover the central nervous system changes contributing to sexual dysfunction in an autoimmune prostatitis model.

Researchers induced an experimental autoimmune prostatitis (EAP) model in rats by injecting a mixture of rat prostate protein and Freund's adjuvant. Comprehensive assessments included H&E and Masson's trichrome staining for histopathology of prostate and penile tissues, ELISA for serum cytokines and neurochemicals, and functional assessment of erectile capability by measuring intracavernous pressure/mean arterial pressure (ICP/MAP) ratio. Mating behavior was analyzed, and brain tissues underwent comprehensive transcriptomic profiling and non-targeted metabolomic analyses to identify central mechanisms.

The EAP rat model successfully demonstrated significant prostatic inflammation and impaired sexual function. Serum analyses revealed elevated pro-inflammatory cytokines, including TNF-α, IL-8, IL-6, and IL-1β. Erectile function was significantly impaired, evidenced by a reduced ICP/MAP ratio, alongside increased penile fibrosis. Mating behavior was also disturbed, with a notably shorter ejaculation latency. Serum neurochemical profiling showed reduced 5-HT and elevated norepinephrine and leptin. Brain transcriptomic analysis identified 557 differentially expressed genes, with significant enrichment in pathways such as cGMP-PKG, calcium, oxytocin, RAP1, and MAPK signaling. Metabolomic analysis further detected 45 differentially abundant metabolites, indicating broad metabolic dysregulation.

The EAP model induced significant prostatic inflammation, impaired erectile function (reduced ICP/MAP ratio), increased penile fibrosis, and disturbed ejaculatory behavior, alongside 557 differentially expressed genes in brain tissue.