Seminal Biomarkers and Sperm Proteomic Signatures Differentiate Acute and Chronic Male Accessory Gland Inflammation

Male accessory gland inflammation (MAGI) comprises a heterogeneous group of inflammatory conditions that may differentially affect the seminal microenvironment and sperm function. However, whether transrectal ultrasound (TRUS)-defined MAGI phenotypes correspond to distinct biological profiles remains insufficiently characterized.

To evaluate whether TRUS-defined phenotypes of MAGI can be discriminated using seminal inflammatory and oxidative stress biomarkers and sperm proteomic profiles, and to assess their potential clinical relevance for disease stratification.

In this case-control study, 20 men with MAGI and 10 healthy controls were enrolled. Patients were classified by TRUS as hypertrophic-congestive (acute) or fibro-sclerotic (chronic) phenotypes. Semen analysis, seminal plasma antioxidant capacity, and sperm lipid peroxidation were assessed. Seminal inflammatory biomarkers were quantified and evaluated by receiver operating characteristic analysis. Proteomic profiling of purified spermatozoa was performed with multivariate and differential expression analyses, followed by functional enrichment and immunofluorescence validation.

Both MAGI phenotypes showed reduced sperm concentration and motility compared with controls, whereas abnormal morphology was more pronounced in the fibro-sclerotic phenotype. Antioxidant capacity was reduced, and lipid peroxidation increased in both groups, with greater oxidative imbalance in the hypertrophic-congestive phenotype. SuPAR discriminated MAGI patients from controls with high specificity, whereas sST2 accurately differentiated acute and chronic phenotypes. Proteomic analysis identified distinct, nonoverlapping molecular signatures across groups. Pathway analysis showed downregulation of proteins involved in sperm function and fertilization, with additional impairment of motility-related processes in the chronic phenotype. Immunofluorescence confirmed reduced expression of a key flagellar structural protein, most markedly in fibro-sclerotic MAGI.

TRUS-defined MAGI phenotypes are associated with distinct biomarker and proteomic profiles, consistent with different inflammatory states and patterns of sperm molecular injury. These findings support a biomarker-assisted approach to phenotype stratification and provide mechanistic insight into inflammation-driven male reproductive dysfunction.