Human sperm binding is mediated by the sialyl-Lewis(x) oligosaccharide on the zona pellucida

• Published in: Science (American Association for the Advancement of Science) 2011-09, Vol.333 (6050), p.1761-1764
• Main Authors: Pang, Poh-Choo, Chiu, Philip C N, Lee, Cheuk-Lun, Chang, Lan-Yi, Panico, Maria, Morris, Howard R, Haslam, Stuart M, Khoo, Kay-Hooi, Clark, Gary F, Yeung, William S B, Dell, Anne
• Format: Article
• Language: English
• Subjects: Antibodies - immunology; Carbohydrate Conformation; Carbohydrate Sequence; Egg Proteins - chemistry; Egg Proteins - metabolism; Female; Fucose - chemistry; Glycoconjugates - metabolism; Humans; Ligands; Male; Membrane Glycoproteins - chemistry; Membrane Glycoproteins - metabolism; Oligosaccharides - chemistry; Oligosaccharides - immunology; Oligosaccharides - metabolism; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - metabolism; Selectins - metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Sperm-Ovum Interactions; Spermatozoa - metabolism; Zona Pellucida - chemistry; Zona Pellucida - metabolism; Zona Pellucida Glycoproteins
• ISSN: 1095-9203
• DOI: 10.1126/science.1207438

Human fertilization begins when spermatozoa bind to the extracellular matrix coating of the oocyte, known as the zona pellucida (ZP). One spermatozoan then penetrates this matrix and fuses with the egg cell, generating a zygote. Although carbohydrate sequences on the ZP have been implicated in sperm binding, the nature of the ligand was unknown. Here, ultrasensitive mass spectrometric analyses revealed that the sialyl-Lewis(x) sequence [NeuAcα2-3Galβ1-4(Fucα1-3)GlcNAc], a well-known selectin ligand, is the most abundant terminal sequence on the N- and O-glycans of human ZP. Sperm-ZP binding was largely inhibited by glycoconjugates terminated with sialyl-Lewis(x) sequences or by antibodies directed against this sequence. Thus, the sialyl-Lewis(x) sequence represents the major carbohydrate ligand for human sperm-egg binding.