Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters.
Comprehensive metabolic profiles of seminal plasma with different forms of male infertility and their correlation with sperm parameters.
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DOI：
10.1016/j.jpba.2019.112888
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发表时间：
2020-01
影响因子：
3.4
通讯作者：
Yamei Xu;Hongmei Lu;Yang Wang;Zhimin Zhang;Qian Wu
中科院分区：
文献类型：
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作者：
Yamei Xu;Hongmei Lu;Yang Wang;Zhimin Zhang;Qian Wu
精浆代谢组学检测广泛应用于男性不育症的诊断和分子机制的发现。然而，到目前为止，分析方法的代谢组覆盖范围的局限性阻碍了全面的代谢物生物标志物的发现。此外，广泛使用的病例对照比较不足以揭示代谢变化与不同精子异常之间的详细相关性。在这项工作中，我们旨在通过液相色谱-质谱（LC-MS）检测，利用先前建立的新的样品制备程序，对健康对照组和不同精液异常的不育病例样本进行全面的精液代谢谱分析，以发现代谢组学差异。通过多因素分析，在检测到的624种代谢物特征中，发现63种不同代谢物类别的潜在生物标志物与精浆不孕症有关。有趣的是，不同的不孕症形式有不同的潜在生物标志物，很少有共同的，大多数潜在的生物标志物是在少弱畸形精子症样本中发现的。为了进一步发现代谢组学变化与特定精子异常的关系，我们还收集了精子浓度、精子畸形率和精子活力等精子参数，并使用多元线性回归来发现精子参数与潜在生物标志物之间的相关性。最后，发现17种代谢物的水平与精子参数显著相关。大多数相关性与先前报道的不孕症机制一致，如酰基肉碱与精子浓度和精子畸形的相关性，以及一些抗氧化剂与精子畸形率和精子活力的相关性。焦磷酸异戊烯基、2-磷酸甘油酸、γ-谷氨酰基-硒-甲基硒代半胱氨酸与精子畸形率呈负相关，肌酸核糖体与精子浓度呈负相关，均为首次报道。所有潜在的生物标志物涉及14条代谢途径，在能量产生、抗氧化、激素调节和精子膜等方面发挥重要作用。这些结果证实了先前报道的分子机制（如氧化应激和能量产生），并为男性不育的病理提供了新的可能线索，对未来男性不育的病因学、诊断和治疗具有指导意义。
Metabolomics measurements of seminal plasma are widely used in diagnosis and finding of molecular mechanisms of male infertility. However, so far the limitation of metabolome coverage of analytical methods hinders comprehensive metabolite biomarker finding. Moreover, the widely used case-control comparison is not enough to unveil the detailed correlations of the metabolic changes with different sperm abnormalities. In this work, we aimed to have comprehensive metabolic profiling of seminal plasma to find the metabolomics difference between healthy controls and infertility case samples with different semen abnormities by liquid chromatography–mass spectrometry (LC–MS) detection with previously established new sample preparation procedure. Among 624 detected metabolite features, 63 potential biomarkers in various metabolite classes were found for infertility in seminal plasma by multivariate analysis. Interestingly, different infertility forms have different potential biomarkers with few in common, and most of potential biomarkers were found in oligo-astheno-teratospermia samples. To further find the association of the metabolomic changes with specific sperm abnormality, sperm parameters including sperm concentration, sperm deformity rate and sperm motility were also collected, and multivariate linear regression was used to find correlations between sperm parameters and potential biomarkers. Finally, levels of 17 metabolites were found to be significantly correlated with sperm parameters. Most of correlations agreed with previously reported mechanisms of infertility, such as correlation of acylcarnitines with sperm concentration and sperm deformity, and correlation of some antioxidants with sperm deformity rate and sperm motility. Some correlations were reported for the first time, such as negative correlations of isopentenyl pyrophosphate, 2-phosphoglyceric acid and γ-glutamyl-Se-methylselenocysteine with sperm deformity rate, and negative correlation of creatine riboside with sperm concentration. All the potential biomarkers were involved in 14 metabolic pathways playing important role in energy production, antioxidation, hormone regulation and sperm membrane. These results proved previously reported molecular mechanism (such as oxidative stress and energy production) and also gave new possible clues to the pathology of male infertility, which will benefit future etiology, diagnosis and treatment of male infertility.