Comprehensive multi-omics analyses elucidate the mechanism of male sexual dysfunction induced by chronic prostatitis/chronic pelvic pain syndrome in the experimental autoimmune prostatitis rat model.

Authors

Jiaochen Luan, Qi Gu, Mengchi Yu, Danni Chen, Chunlu Xu, Jiayi Zhang, Jie Yang, Ninghong Song

Published in

The journal of sexual medicine. Volume 23. Issue 8. Jul 03, 2026.

Abstract

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), characterized by persistent pain, is significantly associated with sexual dysfunction, yet the underlying mechanisms remain poorly understood.
This study sought to elucidate the underlying central mechanisms linking autoimmune prostatitis to sexual dysfunction by employing an integrated multi-omics approach in a well-established rodent model.
An experimental autoimmune prostatitis (EAP) model was induced by injecting a mixture of rat prostate protein and Freund's adjuvant. Comprehensive assessments were conducted, including histopathological evaluation of prostate and penile tissues via H&E and Masson's trichrome staining, quantification of serum cytokines and neurochemicals using ELISA, functional assessment of erectile capability by measuring intracavernous pressure/mean arterial pressure (ICP/MAP) ratio, and detailed mating behavior analysis. Brain tissues from rats were collected for comprehensive transcriptomic profiling and non-targeted metabolomic analyses.
Primary outcomes included brain transcriptomic and metabolomic alterations, mating behavior parameters, erectile function assessed by ICP/MAP measurement, histological changes in prostate and penile tissues, and serum inflammatory cytokine and neurochemical levels.
The EAP model demonstrated significant prostatic inflammation, elevated serum pro-inflammatory cytokines (TNF-α, IL-8, IL-6, IL-1β), impaired erectile function (reduced ICP/MAP ratio), increased penile fibrosis, and disturbed ejaculatory behavior with shorter ejaculation latency. Serum analyses revealed altered neurochemical levels, including reduced 5-HT and elevated norepinephrine and leptin. Transcriptomic analysis identified 557 differentially expressed genes with enrichment in cGMP-PKG, calcium, oxytocin, RAP1, and MAPK signaling pathways. Besides, metabolomic analysis detected 45 differentially abundant metabolites, including key molecules such as N-acetyl-DL-aspartic acid, aspartic acid, threonine, and the nitric oxide pathway intermediate argininosuccinic acid. Integrated pathway analysis highlighted significant alterations in neuroactive ligand-receptor interaction, GABAergic synapse, and glutathione metabolism pathways. Immunofluorescence validation confirmed substantial downregulation of GABAergic proteins (GABRA5, GAD65, VGAT) in the paraventricular nucleus. Furthermore, integrated multi-omics analysis revealed coordinated alterations between gene expression and metabolic profiles.
The identified central GABAergic dysregulation presents a promising therapeutic target for managing CP/CPPS-related sexual dysfunction.
The novel application of integrated brain multi-omics represents a key strength, while limited translational applicability to humans remains a constraint.
Autoimmune prostatitis induces significant central genetic and metabolic alterations that contribute to sexual dysfunction, providing new mechanistic insights and potential therapeutic avenues for this challenging condition.

PMID:
42447397
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.