title: A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility.
abstract: Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures. A galactose-binding protein has been identified in mammalian spermatozoa that has similarity to the well-characterized hepatic asialoglycoprotein receptor. 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 (alpha-tocopherol) to porcine spermatozoa. Treatment of sperm cells with one hybrid polymer in particular produced large increases in intracellular sperm levels of alpha-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.
authors.affiliation: Department of Chemistry, University of Durham, South Road, Durham, DH1 3LE, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Fleming
authors.forename: André
authors.initials: A
authors.lastname: Maldjian
authors.forename: Daniel
authors.initials: D
authors.lastname: Da Costa
authors.forename: Attvinder K
authors.initials: AK
authors.lastname: Rullay
authors.forename: David M
authors.initials: DM
authors.lastname: Haddleton
authors.forename: Justin
authors.initials: J
authors.lastname: St John
authors.forename: Paul
authors.initials: P
authors.lastname: Penny
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Noble
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cameron
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Davis
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D005298:Fertility / Q000187:drug effects* / Q000502:physiology; D005303:Fertility Agents, Male / Q000138:chemical synthesis / Q000494:pharmacology*; D006001:Glycoconjugates / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D015394:Molecular Structure; D011108:Polymers / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D013552:Swine; D024502:alpha-Tocopherol / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D005303:Fertility Agents, Male; D006001:Glycoconjugates; D011108:Polymers; D024502:alpha-Tocopherol