The galectin-1–glycan axis controls sperm fertilizing capacity by regulating sperm motility and membrane hyperpolarization

Lectin–glycan recognition systems play central roles in many physiologic and pathologic processes. We identified a role for galectin-1 (Gal-1), a highly conserved glycan-binding protein, in the control of sperm function. We found that Gal-1 is expressed in the epididymis and associates with sperm during epididymal maturation. Exposure of sperm to Gal-1 resulted in glycan-dependent modulation of the acrosome reaction (AR), a key event in the fertilization process. Gal-1-deficient (Lgals1−/−) mice revealed the essential contribution of this lectin for full sperm fertilizing ability both in vitro and in vivo. Mechanistically, Lgals1−/− sperm exhibited defects in their ability to develop hyperactivation, a vigorous motility required for penetration of the egg vestments. Moreover, Lgals1−/− sperm showed a decreased ability to control cell volume and to undergo progesterone-induced AR, phenotypes that were rescued by exposure of the cells to recombinant Gal-1. Interestingly, the AR defect was associated with a ...