Chronic prostatitis and male infertility: association mechanism and research progress

Objective To systematically examine the association between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and male infertility, elucidate the pathophysiological mechanisms by which CP/CPPS impairs fertility, summarize current research advancements, and establish a foundation for targeted diagnosis and treatment strategies.

This study synthesizes clinical research, meta-analyses, and experimental model evidence to examine alterations in semen parameters (concentration, motility, morphology, DNA fragmentation rate) and seminal plasma biomarkers (PSA, cytokines, hormones). It explores the interactions across various systems, including neuro-immune-endocrine dysregulation, metabolic diseases, microcirculatory dysfunction, aberrant intestinal-prostate axis activity, and mitochondrial autophagy. The study assesses diagnostic frameworks such as NIH-CPSI and UPOINT, along with their therapeutic effectiveness.

CP/CPPS markedly decreased sperm concentration (SMD= – 14.12), forward motility (SMD= – 5.94), and normal morphology rate (SMD= – 8.26), while elevating DNA fragmentation rates (> 30%). Principal mechanisms comprise: (1) Pro-inflammatory cytokines (e.g., IL-6, TNF-α) impairing mitochondrial function and DNA integrity; (2) Neuroendocrine dysfunction inhibiting the hypothalamic-pituitary-testicular axis; (3) Metabolic syndrome comorbidity (OR = 2.10) inducing an energy crisis via mitochondrial dysfunction; (4) Gut microbiota dysbiosis diminishing anti-inflammatory short-chain fatty acids (SCFAs), intensifying systemic and reproductive tract inflammation; (5) Mitophagy impairments (e.g., PINK1 dysfunction) resulting in the accumulation of damaged sperm mitochondria. UPOINTs phenotype-guided multimodal therapy mitigates clinical symptoms, with 77.5% of patients attaining a reduction of at least 6 points in the NIH chronic prostatitis symptom index (NIH-CPSI) scores within 6 months.

The intricate pathogenesis of male infertility in CP/CPPS encompasses a diverse array of pathways: inflammatory, autoimmune, neuroendocrine, metabolic, and mitochondrial. Future investigations should concentrate on the mechanisms of mitochondrial autophagy and the regulation of epigenetics. Clinical management may contemplate the implementation of multidisciplinary, collaborative, phenotype-oriented, comprehensive therapies to disrupt the “chronic pain-inflammation-infertility” vicious cycle and protect fertility health. Similar content being viewed by others Data availability No datasets were generated or analysed during the current study.

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Cells 8(7):712. https://doi.org/10.3390/cells8070712 Author information Authors and Affiliations Contributions Author Contributions StatementQinyu Zhang: Conceptualization, Literature synthesis, Original draft preparation, Visualization.Jintao Shi: Methodology validation, Data curation, Formal analysis, Manuscript editing.Yang Xuan: Resource investigation, Visualization, Writing-review & editing.Yue Duan (Corresponding Author): Supervision, Project administration, Funding acquisition, Critical revision, Manuscript finalization.Hao Zhang (Corresponding Author): Supervision, Validation, Critical revision, Correspondence oversight.All authors contributed to scientific discussion, approved the final manuscript, and agree to be accountable for all aspects of the work. Corresponding authors Ethics declarations Conflict of interest The authors declare no competing interests. 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