Gender-specific glycosylation of human glycodelin affects its contraceptive activity

We have recently demonstrated that a human amniotic fluid-derived glycoprotein, glycodelin-A (GdA; previously known as PP14 or PAEP), potently inhibits gamete binding in an established sperm-egg binding system and expresses immunosuppressive activities directed against a variety of different immune cell types, GdA has high mannose-, hybrid-, and complex-type bi-antennary oligosaccharides including structures with fucosylated or sialylated N,N'-diacetyllactose diamine (GalNAc beta 1-4GlcNAc) sequences, which are rare in other human glycoproteins. We now report the characterization of glycodelin-S (GdS), This is a human seminal plasma glycoprotein that is immunologically indistinguishable from GdA, but unlike the latter, does not inhibit human sperm-zona pellucida binding under hemizona assay conditions. Analysis of the N-glycans of GdS by mass spectrometry revealed that all glycoforms of GdS are different from those of GdA. GdS glycans are unusually fucose-rich, and the major complex-type structures are biantennary glycans with Lewis(x) (Gal beta 1-4(Fuc alpha 1-3)GlcNAc) and Lewis(y) (Fuc alpha 1-2Gal beta 1-4 (Fuc alpha 1-3)GlcNAc) antennae, It is probable that these highly fucosylated epitopes contribute to the immunosuppressive activity of human seminal plasma and to the low immunogenicity of sperm, This study provides the first evidence for gender-specific glycosylation that may serve to regulate key processes involved in human reproduction.