Gary F Clark1. 1. 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
Abstract
STUDY QUESTION: What is the role of carbohydrates in the binding of human sperm to the zona pellucida (ZP) and what are potential implications for pathogenesis? SUMMARY ANSWER: Both lectin-like and protein-protein interactions play an essential role in human gamete interactions. WHAT IS KNOWN ALREADY: Studies in the mouse and human indicate a role for both lectin-like and protein-protein interactions during sperm binding to the ZP. STUDY DESIGN, SIZE, DURATION: Non-systematic literature review. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): 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.
STUDY QUESTION: What is the role of carbohydrates in the binding of human sperm to the zona pellucida (ZP) and what are potential implications for pathogenesis? SUMMARY ANSWER: Both lectin-like and protein-protein interactions play an essential role in human gamete interactions. WHAT IS KNOWN ALREADY: Studies in the mouse and human indicate a role for both lectin-like and protein-protein interactions during sperm binding to the ZP. STUDY DESIGN, SIZE, DURATION: Non-systematic literature review. MAIN RESULTS AND THE ROLE OF CHANCE: 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. LIMITATIONS, REASONS FOR CAUTION: 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. WIDER IMPLICATIONS OF THE FINDINGS: 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. STUDY FUNDING/COMPETING INTEREST(S): 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: Zhigang Wu; Yunpeng Liu; Cheng Ma; Lei Li; Jing Bai; Lauren Byrd-Leotis; Yi Lasanajak; Yuxi Guo; Liuqing Wen; He Zhu; Jing Song; Yanhong Li; David A Steinhauer; David F Smith; Baohua Zhao; Xi Chen; Wanyi Guan; Peng George Wang Journal: Org Biomol Chem Date: 2016-11-29 Impact factor: 3.876