A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility
A carbohydrate-antioxidant hybrid polymer reduces oxidative damage in spermatozoa and enhances fertility
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DOI：
10.1038/nchembio730
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发表时间：
2005-10-01
影响因子：
14.8
通讯作者：
Davis, BG
中科院分区：
文献类型：
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作者：
Fleming, C;Maldjian, A;Davis, BG
配子-配子相互作用受到碳水化合物-蛋白质相互作用的关键调节，碳水化合物-蛋白质相互作用依赖于多价碳水化合物结构的碳水化合物选择性识别（1，2）。在哺乳动物精子中发现了一种半乳糖结合蛋白（3），与肝脏去唾液酸糖蛋白受体（4）具有相似性。为了利用这类蛋白质结合和内化显示半乳糖的大分子的能力，我们设计了混合碳水化合物-抗氧化剂聚合物来向猪精子提供抗氧化剂维生素E（α-生育酚）。特别是用一种杂交聚合物处理精子细胞产生了α-生育酚的细胞内精子水平的大幅增加，并大大降低了氧化应激下的内源性脂肪酸降解。聚合物处理的精子具有增强的生理特性和更长的半衰期，从而提高受精率。我们的研究结果表明，混合聚合物递送系统可以延长哺乳动物精子的功能活力和提高生育率，我们的功能指导优化策略可以应用于发现活性糖缀合物配体。
Gamete-gamete interactions are critically modulated by carbohydrate-protein interactions that rely on the carbohydrate-selective recognition of polyvalent carbohydrate structures(1,2). A galactose-binding protein has been identified in mammalian spermatozoa(3) that has similarity to the well-characterized hepatic asialoglycoprotein receptor(4). 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.