title: The role of carbohydrate recognition during human sperm-egg binding.
abstract: OBJECTIVE
  What is the role of carbohydrates in the binding of human sperm to the zona pellucida (ZP) and what are potential implications for pathogenesis?
  
  
  CONCLUSIONS
  Both lectin-like and protein-protein interactions play an essential role in human gamete interactions.
  
  
  BACKGROUND
  Studies in the mouse and human indicate a role for both lectin-like and protein-protein interactions during sperm binding to the ZP.
  
  
  METHODS
  Non-systematic literature review.
  
  
  RESULTS
  Ultrasensitive analysis by mass spectrometry of glycans linked to the human ZP has confirmed that this matrix is coated with a high density of complex type N-glycans terminated with the sialyl-Lewis(x) (sLe(x)) sequence, the universal selectin ligand. Selectins are essential for lymphocyte homing, and they participate in the initial binding of circulating leukocytes to activated endothelium at the sites of infection and tissue injury. Subsequent inhibition studies confirmed that either the sLe(x) tetrasaccharide or neoglycoproteins terminated with this sequence inhibited human sperm-ZP binding by 70% in the hemizona assay. These results support the hypothesis that both lectin-like and protein-protein interactions play an essential role in human gamete interactions. The sLe(x) sequence is also a ligand for siglec-9, a lectin-bearing immunoreceptor tyrosine-based inhibitory motif that transmits inhibitory signals. This siglec is expressed on a wide variety of different types of human leukocytes and lymphocytes. This result is consistent with the hypothesis that human ZP glycans are also being employed for immune recognition of the egg and the histoincompatible embryo prior to blastocyst hatching.
  
  
  CONCLUSIONS
  This field of study is complex and more experimental work is needed to reveal fully the mechanism of sperm-ZP binding and how it varies between species.
  
  
  CONCLUSIONS
  Knowledge about the glycans involved in sperm-egg binding may be relevant to infertility due to fertilization failure and also to the mother's immune tolerance of the preimplantation embryo.
  
  
  BACKGROUND
  Studies focused on human sperm-egg interactions carried out by the author and coworkers have been supported by the Life Sciences Mission Enhancement Reproductive Biology Program funded by the State of Missouri, a Research Board Grant (CB000500) supported by the University of Missouri System and a grant from the Jeffress Memorial Trust of Virginia. Support from the Breeden-Adams Foundation has also been obtained to investigate potential linkages to tumor evasion. The author has no conflict of interest to declare.
authors: Division of Reproductive Medicine and Fertility, and Division of Reproductive and Perinatal Research, Department of Obstetrics, Gynecology and Women's Health, University of Missouri School of Medicine, Columbia, MO 65212, USA. clarkgf@health.missouri.edu
authors: Gary F
authors: GF
authors: Clark
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D005260:Female; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013084:Sperm-Ovum Interactions; D015044:Zona Pellucida / Q000276:immunology / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D037102:Lectins; D009844:Oligosaccharides; D011134:Polysaccharides; C412227:SIGLEC9 protein, human; D019087:Selectins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D000080506:Sialyl Lewis X Antigen