Sperm fucosyltransferase-5 interacts with oviductal cell membrane proteins to protect human spermatozoa from oxidative stress

Abstract

One of the major causes of sperm dysfunction is oxidative stress arising as a result of excessive production of reactive oxygen species. Oxidative stress is associated with cell damage, lipid peroxidation, DNA fragmentation, impaired fertilization ability of spermatozoa and lower pregnancy rates after IVF. In mammals, including human, the oviduct functions as a sperm reservoir which is created by binding of the sperm to the epithelial lining in the isthmic region of the oviduct. Sperm-oviductal epithelial cell interaction maintains/improves the motility, preserves the viability and fertilizing ability and reduces sperm chromatin damage in vivo and in vitro. However, the underlying mechanism(s) by which the spermatozoa-oviduct interaction producing these beneficial effects remains to be elucidated. One possibility is that oviduct protects spermatozoa from oxidative stress. We identified sperm fucosyltransferase-5 (sFUT5) as a surface zona pellucida receptor locating on the acrosomal region of human spermatozoa. Our unpublished data further demonstrated that affinity-purified sFUT5 bound to the epithelial lining of human oviduct and to an immortalized human oviductal epithelial cell line, OE-E6/E7. Thus, we hypothesize that sFUT5 mediates spermatozoa-oviductal epithelial cells interaction and the beneficial effects of such interaction on the fertilizing ability of human spermatozoa. In this project, oviductal epithelial cell membrane protein (OEMP) was extracted from OE-E6/E7 cells. Pretreatment of the OEMP significantly protected the sperm from the adverse effect of H2O2 on motility, membrane integrity, and DNA integrity as determined by computer assisted sperm analysis, Bodipy C11-based lipid peroxidation assay, and Comet assay respectively. The inclusion of antisFUT5 antibody or purified sFUT5 significantly suppressed the protective effects of OEMP. In contrast, asialofetuin, a reported sFUT5 substrate, was able to partly mimic the protective effect of OEMP. In conclusion, OEMP may interact with sFUT5 to maintain sperm functions by protecting the sperm from oxidative damage. The results provide a scientific basis for the use of OEMP or sFUT5-interacting proteins to maintain/improve the fertilization potential of human spermatozoa in vitro.