Sulfogalatosylglycerolipid (SGG, aka sminolipid) is a sulfoglycolipid present selectively on the mammalian sperm suface. We ha shown that SGG is important for sperm-ZP/egg plasma membrane binding. Ironically, SGG ad its analog, sulfogalactosylceramide (SGC), which is present on the vaginal/cervical ephitelial cell surface, also have affinity for a number of microbes and virus and their surface proteins. The interaction with microbes and viruses with diverse consequences to the cells, however, may be prevented by the interaction of these sulfoglycolipids with cationic antimicrobial peptides(AMPs). We have recently demonstred the affinity of SGG/SGC for two AMPs, Bin1b (6 kDa) and LL-37 (3.7 kDa)are a b-defensin and a-defensin family member of AMPs, respectively. Both b-defensin and hCAP18, LL-37 precursor, are expressed in high amounts in the epididymis. However, since SGG exist in abundance on the sperm plasma membrane (10% of total lipids), mature caudal epididymal sperm could still receive more of these cationic AMPs onto the sperm surface, thes resulting in the masking of SGG. In fact, these AMP-treated mouse sperm had decreased ability to fertilize eggs in an AMP-concetration dependent manner, presumably due to the blocking of sperm SGG to interact with the ZP and egg plasma membrane. LL-37 had a greater potency in this inhibition than Bin1b. At 16 micro-g/ml of exogenous LL-37, sperm had zero ability to fertilize the eggs. In contrast, eggs were still fertilzed at 50% contol values when incubate with sperm treated with 106 micro-g/ml of Bin1b. The higher inhibitory action of LL-37 in fertilization was due to its adverse effects on sperm motility an viability. Regardless, LL-37 di not induce any cell death to both human vaginal and cervical epithelial cell lenes. Therefore, it is promising from our results that LL-37 and Bin1b could be used as vaginal non-hormonal contraceptives with additional microbicidal activity.
Contraceptive actions of Bin1b and LL-37 antimicrobial peptide : involvement of sperm sulfogalactosylglycerolipid (SGG) / H. Xu, G. Hommalai, S. Hu, R. DI BRISCO, D. Fongmoon, P. Nyholm, F.C.V. Ronchetti, R. Hancock, S. Hall, Y. Zhang, N. Tanphaichitr. ((Intervento presentato al 3. convegno Sino-Canada Bilateral Workshop on Reproductive Healt Reasearch tenutosi a Nanjing nel 2009.
Contraceptive actions of Bin1b and LL-37 antimicrobial peptide : involvement of sperm sulfogalactosylglycerolipid (SGG)
R. DI BRISCO;F.C.V. Ronchetti;
2009
Abstract
Sulfogalatosylglycerolipid (SGG, aka sminolipid) is a sulfoglycolipid present selectively on the mammalian sperm suface. We ha shown that SGG is important for sperm-ZP/egg plasma membrane binding. Ironically, SGG ad its analog, sulfogalactosylceramide (SGC), which is present on the vaginal/cervical ephitelial cell surface, also have affinity for a number of microbes and virus and their surface proteins. The interaction with microbes and viruses with diverse consequences to the cells, however, may be prevented by the interaction of these sulfoglycolipids with cationic antimicrobial peptides(AMPs). We have recently demonstred the affinity of SGG/SGC for two AMPs, Bin1b (6 kDa) and LL-37 (3.7 kDa)are a b-defensin and a-defensin family member of AMPs, respectively. Both b-defensin and hCAP18, LL-37 precursor, are expressed in high amounts in the epididymis. However, since SGG exist in abundance on the sperm plasma membrane (10% of total lipids), mature caudal epididymal sperm could still receive more of these cationic AMPs onto the sperm surface, thes resulting in the masking of SGG. In fact, these AMP-treated mouse sperm had decreased ability to fertilize eggs in an AMP-concetration dependent manner, presumably due to the blocking of sperm SGG to interact with the ZP and egg plasma membrane. LL-37 had a greater potency in this inhibition than Bin1b. At 16 micro-g/ml of exogenous LL-37, sperm had zero ability to fertilize the eggs. In contrast, eggs were still fertilzed at 50% contol values when incubate with sperm treated with 106 micro-g/ml of Bin1b. The higher inhibitory action of LL-37 in fertilization was due to its adverse effects on sperm motility an viability. Regardless, LL-37 di not induce any cell death to both human vaginal and cervical epithelial cell lenes. Therefore, it is promising from our results that LL-37 and Bin1b could be used as vaginal non-hormonal contraceptives with additional microbicidal activity.
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