Abstract
Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures1,2. A galactose-binding protein has been identified in mammalian spermatozoa3 that has similarity to the well-characterized hepatic asialoglycoprotein receptor4. With the aim of exploiting the ability of this class of proteins to bind and internalize macromolecules displaying galactose, we designed hybrid carbohydrate-antioxidant polymers to deliver antioxidant vitamin E (α-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one hybrid polymer in particular produced large increases in intracellular sperm levels of α-tocopherol and greatly reduced endogenous fatty acid degradation under oxidative stress. The polymer-treated spermatozoa had enhanced physiological properties and longer half-lives, which resulted in enhanced fertilization rates. Our results indicate that hybrid polymer delivery systems can prolong the functional viability of mammalian spermatozoa and improve fertility rates, and that our functionally guided optimization strategy can be applied to the discovery of active glycoconjugate ligands.
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Acknowledgements
We would like to thank JSR Healthbred and the UK Department of Trade and Industry (DTI) for funding (DTI Smart Award), R. Hunter (Unilever) for advice and technical assistance with GPC determinations, K. Harrison for video assistance, and M. Alvarez-Reyes for assistance with confocal microscopy.
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A.M., P.P. and R.C.N. are/have been employees of JSR Healthbred who may have longer-term goals in exploiting this technology. An initial patent application has now lapsed.
Supplementary information
Supplementary Table 1
Composition of terpolymers. (PDF 59 kb)
Supplementary Video 1
Treated sperm at Day 3. (MOV 8496 kb)
Supplementary Video 2
Untreated sperm at Day 3. (MOV 7421 kb)
Supplementary Scheme 1
Monomer synthesis. (PDF 82 kb)
Supplementary Scheme 2
Polymer synthesis. (PDF 94 kb)
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Fleming, C., Maldjian, A., Da Costa, D. et al. A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility. Nat Chem Biol 1, 270–274 (2005). https://doi.org/10.1038/nchembio730
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DOI: https://doi.org/10.1038/nchembio730
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