License to bind: Role of glycoproteins in male (in)fertility

Male infertility affects 16.9% of couples and accounts for up to 30% of infertility cases. Its causes include genetic, acquired, and idiopathic factors, as well as environmental exposures and lifestyle habits like smoking and poor diet. Conventional semen analysis remains the gold standard but provides limited insight into molecular mechanisms and often fails to explain subfertility. Fertilization requires complex biochemical changes in spermatozoa, such as capacitation and the acrosome reaction, dependent on protein and glycoprotein interactions. Altered glycosylation patterns are linked to impaired capacitation, reduced fertilization potential, and disrupted spermatozoa-oocyte interactions. Specific glycoproteins, including clusterin, fibronectin, glycodelin-S, and others, are emerging as diagnostic and prognostic biomarkers. This review focuses on the structure, function, and glycosylation of glycoproteins in human semen, emphasizing their impact on male reproductive health and fertility. Their characterization offers new insights for understanding infertility and developing biomarkers for improved spermatozoa selection in assisted reproductive technologies.