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Comprehensive assessments were conducted, including histopathological evaluation of prostate and penile tissues via H&amp;E and Masson\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcomes<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The EAP model demonstrated significant prostatic inflammation, elevated serum pro-inflammatory cytokines (TNF-\u03b1, IL-8, IL-6, IL-1\u03b2), 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Implications<\/jats:title>\n                    <jats:p>The identified central GABAergic dysregulation presents a promising therapeutic target for managing CP\/CPPS-related sexual dysfunction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Strengths &amp; Limitations<\/jats:title>\n                    <jats:p>The novel application of integrated brain multi-omics represents a key strength, while limited translational applicability to humans remains a constraint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jsxmed\/qdag160","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T11:44:40Z","timestamp":1778154280000},"source":"Crossref","is-referenced-by-count":0,"title":["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"],"prefix":"10.1093","volume":"23","author":[{"given":"Jiaochen","family":"Luan","sequence":"first","affiliation":[{"name":"Department of Urology, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research , Nanjing , Jiangsu, 210009,","place":["China"]},{"name":"Department of Urology, Jiangsu Provincial People\u2019s 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210029,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Children's Hospital of Nanjing Medical University , Nanjing , Jiangsu, 210008,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunlu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Andrology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, 210008, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Jiangsu Provincial People\u2019s Hospital, The First Affiliated Hospital of Nanjing Medical University , Nanjing , Jiangsu, 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