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 biantennary oligosaccharides including structures with fucosylated or sialylated N, N'-diacetyllactosediamine (GalNAcbeta1-4GlcNAc) 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 Lewisx (Galbeta1-4(Fucalpha1-3)GlcNAc) and Lewisy (Fucalpha1-2Galbeta1-4(Fucalpha1-3)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.
Morris
H R
HR
Department of Biochemistry, Imperial College, London SW7 2AY, United Kingdom. a.dell@ic.ac.uk
Dell
A
A
Easton
R L
RL
Panico
M
M
Koistinen
H
H
Koistinen
R
R
Oehninger
S
S
Patankar
M S
MS
Seppala
M
M
Clark
G F
GF
D003270:Contraceptive Agents / Q000378:metabolism*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D000071816:Glycodelin; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D008958:Models, Molecular; D011257:Pregnancy Proteins / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013056:Spectrophotometry, Ultraviolet; D013084:Sperm-Ovum Interactions / Q000187:drug effects
D003270:Contraceptive Agents; D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins