Abstract
Urinary tract infections caused by uropathogenic Escherichia coli (UPEC) pathovars belong to the most frequent infections in humans. 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, the fertility of patients can be permanently impaired. Because a 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. In UPEC-elicited acute epididymitis in mice, a substantial loss of N-acetylneuraminic acid residues was detected in epididymal spermatozoa and epithelial cells using combined laser microdissection/HPLC-ESI-MS analysis. 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. In vitro, such an UPEC induced N-acetylneuraminic acid 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 a premature acrosome reaction during acute epididymitis.
Highlights
Acute epididymitis or a combined epididymo-orchitis in men represents a relevant entity in urological practice
N-acetylneuraminic acid (Neu5Ac) as well as N-glycolylneuraminic acid (Neu5Gc) are the most abundant species in mammals. These sugar residues are commonly linked to the outermost position of the largest share of glycoproteins, which places them in an ideal position for their indispensable role in a diverse range of cellular processes such as intercellular adheacid-binding immunoglobulin-type lectin; SNA, Sambucus nigra; LCMD, laser capture microdissection; KDO, 3-deoxy-D-manno-oct-2-ulosonic acid; DANA, N-acetyl-2,3-dehydro-2-deoxyneuraminic acid; keto-3-deoxynononic acid (KDN), 2-keto-3deoxynononic acid; HTF, human tubal fluid; PSA, Pisum sativum; DMB, 4,5methylene dioxybenzene
Desialylation of Spermatozoa and Epithelial Cells Is a Consequence of Uropathogenic Escherichia coli (UPEC) Infection in the Epididymitis Mouse Model— To elucidate whether the UPEC-induced acrosome reaction leads to an activation of endogenous sialidases, initiating a subsequent desialylation of spermatozoa, an established epididymitis mouse model was utilized [25]
Summary
Acute epididymitis or a combined epididymo-orchitis in men represents a relevant entity in urological practice. Recent data revealed that, during capacitation, a biochemical process in the female reproductive tract in which spermatozoa accomplish full fertilizing “capacity,” two sialidases (the neuraminidases NEU1 and NEU3) are shed from the surface of spermatozoa, likely by the activity of proteases, which could be efficiently counteracted by protease inhibitors [10] This process led to the release of sialic acid residues from the surface of spermatozoa [10]. Several pathogenic bacteria secrete sialidases as a virulence factor, leading to sepsis as a consequence of an uncontrolled stimulation of the immune system In this regard, bacterial sialidase inhibitors can efficiently counteract the dramatic progression of the disease in a mouse model, demonstrating their clinical potential during infection [23, 24]. In consideration that UPEC infection of the epididymis results in a premature release of acrosomal content [5], we aimed to investigate whether this affects the sialome of spermatozoa and surrounding epididymal epithelial cells using a mouse epididymitis model and ejaculates of men with a recent history of the disease
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