OLIGOSACCHARIDE CONSTRUCTS WITH DEFINED STRUCTURES THAT INHIBIT BINDING OF MOUSE SPERM TO UNFERTILIZED EGGS IN-VITRO

During fertilization in mice, free-swimming sperm bind to mZP3, an 83- kDa glycoprotein present in the egg extracellular coat, the zona pellu cida [Wassarman, P. M. (1990) Development 108, 1-17]. Mouse sperm reco gnize and bind to a specific class of serine/threonine-linked (O-linke d) oligosaccharides present on mZP3. After binding to mZP3, sperm unde rgo a form of cellular exocytosis, the acrosome reaction, thereby enab ling them to penetrate the tons pellucida and fertilize the egg. Thus, gamete interactions in mice are carbohydrate-mediated In this context , we tested 15 O-linked-related oligosaccharide constructs with define d structures for their ability to inhibit binding of mouse sperm to ov ulated eggs and to induce sperm to undergo the acrosome reaction in vi tro. Thirteen of the oligosaccharides were constructed and characteriz ed in our laboratory [Seppo, A., Pentilla, L., Niemela, R., Maaheimo, H., Renkonen, O., and Keane, A. (1995) Biochemistry 34, 4655-4661]; tw o were obtained commercially. We found that, while none of the oligosa ccharides induced sperm to undergo the acrosome reaction, a few of the m inhibited binding of sperm to eggs at relatively low concentrations (ID50 < 5 mu M). In certain cases, sperm formed head-to-head aggregate s in the presence of the oligosaccharides. The results suggest that th e ability of oligosaccharides to inhibit binding of sperm to eggs is d ependent on several parameters, including the size and branching patte rn of the oligosaccharide, as well as on the nature of the sugar resid ue at the nonreducing end of the oligosaccharide.