The mechanisms of inhibition of fertilization and activation of development by fertilinβ derived oligopeptide polymers
The sperm protein fertilinβ, a member of the ADAM family of proteins, is implicated in sperm-egg binding in all mammals studied to date. Multivalent inhibitors containing the three-amino acid binding sequence of sperm fertilinβ disintegrin domain, Glu-Cys-Asp (ECD), are effective inhibitors of fertilization. We probed sperm-egg interactions by designing, synthesizing and testing a variety of molecular probes incorporating the ECD peptide in vitro. Evidence suggests that egg integrin α6β 1 functions in the fertilization pathway. We investigated the role of β 1 integrin in mammalian fertilization and the mode of inhibition of fertilin β derived polymers. We determined that polymers displaying the ECD peptide from the fertilinβ disintegrin domain mediate inhibition of mammalian fertilization through a β1 integrin receptor on the egg surface. Inhibition of fertilization is a consequence of competition with sperm binding to the cell surface, not activation of an egg-signaling pathway. Sperm binding to β1 integrin on the egg increases the rate of sperm attachment to the egg surface, but does not increase the number of sperm that attach or fuse.