In mammals, glycoconjugates (e.g. O-glycans, three major classes of N-glycans) coat the surface of sperm. Terminal sialic acid residues and/or fucose act immunosuppressive and facilitate the survival in the female reproductive organs. Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in human. In men, pathogens can also spread to the genital tract via the continuous ductal system eliciting bacterial prostatitis and/or epididymo-orchitis. Antibiotic treatment usually clears pathogens in acute epididymitis, however, fertility of patients can be permanently impaired. Since premature acrosome reaction was observed in an UPEC epididymitis mouse model and sialidases on the sperm surface are considered to be activated via proteases of the acrosome, we aimed to investigate whether alterations of the sialome of epididymal spermatozoa and surrounding epithelial cells occur during UPEC infection. We found a massive redecoration of sperm N-glycans, especially hyposialylation, along with an acrosome reaction induced in vitro. In UPEC elicited acute epididymitis in mouse, a substantial loss of N-acetylneuraminic acid (Neu5Ac) residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. Lectin staining suggested that infection reduced substantially alpha2,6-linked Neu5AC in mouse epididymis and sperm. In support, a substantial reduction of sialic acid residues bound to the surface of spermatozoa was documented in men with a recent history of E. coli associated epididymitis concurrent with premature acrosome reaction. In vitro, such an UPEC induced Neu5Ac release from human spermatozoa was effectively counteracted by a sialidase inhibitor. These findings strongly suggest a substantial remodeling of the glycocalyx of spermatozoa and epididymal epithelial cells by endogenous sialidases after premature acrosome reaction during acute epididymitis.
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