Metabolic characterization of asthenozoospermia using nontargeted seminal plasma metabolomics

Background: Asthenozoospermia (AS) is a common cause of male infertility. Due to the limitation of routine semen analysis, metabolic alterations associated with the disease are unclear. We applied a metabolic profiling strategy as a surrogate method to accurately assess and provide new insights into the etiologies of asthenozoospermia.Methods: Seminal plasma samples from patients diagnosis with asthenozoospermia (n = 33) and healthy subjects (n = 30) were investigated using a nontargeted metabolomics approach based on proton nuclear magnetic resonance (H-1 NMR) spectroscopy. The spectral data were then subjected to multivariate and univariate analyses to identify metabolites that were correlated with asthenozoospermia. The disturbed metabolic pathways which the biomarkers were involved in were analyzed.Results: Nineteen metabolites including up-regulation or down-regulation of several amino acids, changes in lipids metabolism, phospholipids (choline) metabolism, cholesterol metabolism, nucleoside metabolism, the Krebs cycle and energy metabolism were identified and associated with asthenozoospermia. In particular, the elevation of oxysterols such as 5 alpha-cholesterol and 7-ketocholesterol in seminal plasma of patients with asthenozoospermia was an important finding, indicating the important role-of oxidative stress in the mechanism of asthenozoospermia.Conclusions: The excellent performance of this metabolomics approach offer a highly novel means of etiological diagnosis of asthenozoospermia. (C) 2015 Elsevier B.V. All rights reserved.

背景：弱精子症（AS）是男性不育的常见原因。由于常规精液分析的局限性，与该疾病相关的代谢变化尚不明确。我们应用代谢谱分析策略作为一种替代方法，以准确评估弱精子症的病因并提供新的见解。 方法：采用基于质子核磁共振（H - 1 NMR）光谱的非靶向代谢组学方法，对诊断为弱精子症的患者（n = 33）和健康受试者（n = 30）的精浆样本进行研究。然后对光谱数据进行多变量和单变量分析，以识别与弱精子症相关的代谢物。分析生物标志物所涉及的紊乱代谢途径。 结果：鉴定出19种代谢物与弱精子症相关，包括几种氨基酸的上调或下调、脂质代谢、磷脂（胆碱）代谢、胆固醇代谢、核苷代谢、三羧酸循环和能量代谢的变化。特别是，弱精子症患者精浆中氧甾醇如5α - 胆固醇和7 - 酮胆固醇的升高是一项重要发现，表明氧化应激在弱精子症机制中具有重要作用。 结论：这种代谢组学方法的出色性能为弱精子症的病因诊断提供了一种全新的手段。（C）2015爱思唯尔B.V. 版权所有。