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Fertilin is a protein initially identified in guinea pig spermatozoa; it is the prototype of a larger family of conserved proteins designated as a disintegrin and a metalloproteinase (ADAM). These heterodimers which consist of α and β subunits, containing metalloproteinase-like and disintegrin-like domains, appear to play a role in mammalian fertilization. Peptides derived from the disintegrin domains of two ADAMs, fertilin and cyritestin, interfere with gamete adhesion and sperm-egg membrane fusion in non-human species. It has been suggested that fertilin-β binds to an oolemmal integrin, and it is proposed that the tripeptide FEE (Phe-Glu-Glu) is the integrin recognition sequence in human fertilin-β. We evaluated whether fertilin β plays a role in human fertilization by studying the effects of a linear octapeptide containing the FEE sequence, SFEECDLP, and a scrambled octapeptide with the same amino acids, SFPCEDEL, on the incorporation of human spermatozoa by human zona-free eggs. The effects of G4120, a potent RGD-containing (Arg-Gly-Asp) thioether-bridged cyclic peptide which blocks both fibronectin and vitronectin receptors, and the relationship between FEE- and RGD-receptor interactions on sperm-egg interactions were also studied. The FEE-containing peptide, but not the scrampled peptide, inhibited sperm adhesion to oocytes and their penetration, over the range 1-5 μM. The inhibition induced by SFEECDLP was reversible and occurred only in the presence of peptide itself. The G4120 peptide exhibited 10-fold less inhibitory effects on sperm adhesion and penetration than did SFEECDLP. When combined, SFEECDLP and G4120 exhibited strong inhibition of both adhesion and penetration at concentrations that individually had been ineffective, suggesting co-operation between the two receptor-ligand interactions during fertilization. We propose that a fertilin-like molecule is functionally active on human spermatozoa and that its inter... [ABSTRACT FROM AUTHOR]

Fertilin is a protein initially identified in guinea pig spermatozoa; it is the prototype of a larger family of conserved, proteins designated as a disintegrin and a metalloproteinase (ADAM). These heterodimers which consist of alpha and beta subunits, containing metalloproteinase-like and disintegrin-like domains, appear to play a role in mammalian fertilization. Peptides derived from the disintegrin domains of two ADAMs, fertilin and cyritestin, interfere with gamete adhesion and sperm-egg membrane fusion in non-human species. It has been suggested that fertilin-beta binds to an oolemmal integrin, and it is proposed that the tripeptide FEE (Phe-Glu-Glu) is the integrin recognition sequence in human fertilin-beta. We evaluated whether fertilin beta plays a role in human fertilization by studying the effects of a linear octapeptide containing the FEE sequence, SFEECDLP, and a scrambled octapeptide with the same amino acids, SFPCEDEL, on the incorporation of human spermatozoa by human zona-free eggs. The effects of G4120, a potent RGD-containing (Arg-Gly-Asp) thioether-bridged cyclic peptide which blocks both fibronectin and vitronectin receptors, and the relationship between FEE- and RGD-receptor interactions on sperm-egg interactions were also studied. The FEE-containing peptide, but not the scrampled peptide, inhibited sperm adhesion to oocytes and their penetration, over the range 1-5 microM. The inhibition induced by SFEECDLP was reversible and occurred only in the presence of peptide itself. The G4120 peptide exhibited 10-fold less inhibitory effects on sperm adhesion and penetration than did SFEECDLP. When combined, SFEECDLP and G4120 exhibited strong inhibition of both adhesion and penetration at concentrations that individually had been ineffective, suggesting co-operation between the two receptor-ligand interactions during fertilization. We propose that a fertilin-like molecule is functionally active on human spermatozoa and that its interaction with an oolemmal integrin receptor plays a role in fertilization in humans.

Objective: To determine whether human spermatozoa and oocytes share common antigenic epitopes, supporting the hypothesis that their cross-linking by antisperm antibodies present in the clinical sera of infertile couples could promote sperm adhesion to the oolemma., Design: Human and hamster eggs were studied for the presence of antigens recognized by a panel of World Health Organization Task Force monoclonal antibodies (mAbs) originally raised against human spermatozoa. A new technique was devised, using frozen sections of paraformaldehyde-fixed individual human and hamster eggs, to screen rapidly antisperm mAbs for egg reactivity. Living zona-free human and hamster eggs then were exposed to Covaspheres (Duke Scientific, Palo Alto, CA) coupled with these mAbs to document the presence of reactive epitopes on the oolemma., Setting: Academic research environment., Main Outcome Measure(s): Indirect immunofluorescence and Covasphere rosetting., Result(s): Eleven of 37 antisperm mAbs tested reacted with fixed hamster eggs and 10 reacted with human eggs. Five of 6 mAbs reactive with both fixed eggs also reacted with the oolemma of living, zona-free eggs., Conclusion(s): Common antigenic epitopes, some of which are shared with somatic tissues, exist on the oolemma of human eggs and on the plasma membrane of human spermatozoa.