The role of carbohydrate recognition during human sperm-egg binding

What is the role of carbohydrates in the binding of human sperm to the zona pellucida (ZP) and what are potential implications for pathogenesis? Both lectin-like and proteinprotein interactions play an essential role in human gamete interactions. Studies in the mouse and human indicate a role for both lectin-like and proteinprotein interactions during sperm binding to the ZP. Non-systematic literature review. 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 spermZP binding by 70 in the hemizona assay. These results support the hypothesis that both lectin-like and proteinprotein 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. This field of study is complex and more experimental work is needed to reveal fully the mechanism of spermZP binding and how it varies between species. Knowledge about the glycans involved in spermegg binding may be relevant to infertility due to fertilization failure and also to the mothers immune tolerance of the preimplantation embryo. Studies focused on human spermegg 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.