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Lysophospholipids, species-independent markers of pathological changes of spermatozoa

溶血磷脂，精子病理变化的物种独立标记物

基本信息

批准号：
176888449
负责人：
Dr. Karin Müller
金额：
--
依托单位：
Leibniz-Institut für Zoo- und Wildtierforschung (IZW)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2010
资助国家：
德国
起止时间：
2009-12-31 至 2019-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/176888449?language=en
关键词：
Lysophospholipids species independent markers pathological

项目摘要

The impaired sperm quality as a consequence of oxidative stress refers to an increasing problem of reproduction in human as well as stock and wild life.Within the first research period of the project it has been tried to identify a unifying lipid biomarker for all species using mass spectrometry. Especially lysophosphatidylcholine (LPC) has been in favor due to its generation via reactive oxygen species as well as via activation of phospholipases to facilitate the breakdown of oxidized fatty acids. However, we revealed that LPC is accumulating under specific circumstances only, indicating the fact that LPC might not be used as the unifying biomarker. It is therefore assumed that the accumulation of LPC in ejaculates is prevented by a so far unknown mechanism. There are data that re-acetylation of LPC to phosphatidylcholine (PC) and degradation of LPC to water soluble glycerophosphorylcholine (GPC) representing highly effective pathways with huge capacities. This is underlined by the fact, that seminal plasma does provide an enormous anti oxidative potential.Hence, our proposal is focused to investigate further in-vivo mechanisms which do prevent degradation of LPC in sperm samples of various species and intra-individually.We aiming at investigation of cattle-, pig- and feline ejaculates in relation to human samples hence the former do contain ether lipids. The anti-oxidative potential of the latter is so far poorly understood.As a consequence of the results gained during the last research period the focus needs to include not only the investigation of LPC generation. It is believed that during the generation of ROS lipidoxidation products of higher molecular weight (e.g. peroxides or chlorhydrides) are generated.Unstable esther bondings of those lipid oxidation products of higher molecular weight are most probably hydrolyzed by phospholipases, which we are planning to investigate quantitatively. The detection of re-acetylation and further conversion to water soluble end-products of LPC shall be performed using stable isotope labelled molecules (e.g. 13C labelled fatty acids). Those MS- and NMR- investigations shall be embedded within other methods like calorimetry (measurement of anti-oxidative potential), biophysical determinations of sperm membrane structures to analyze the changes of the lipid composition during pathological processes. It is expected that information of lipid composition changes during pathologies can be gained. Furthermore these data will help to understand how those changes influence the sperm quality on a species specific level.

氧化应激导致的精子质量受损是人类以及家畜和野生动物日益严重的生殖问题。在项目的第一个研究阶段，已经尝试使用质谱法确定所有物种的统一脂质生物标志物。尤其是溶血磷脂酰胆碱（LPC），由于其通过活性氧以及磷脂酶的激活来促进氧化脂肪酸的分解而受到青睐。然而，我们发现LPC仅在特定情况下积累，这表明LPC可能不能作为统一的生物标志物。因此，假设射精中LPC的积累是由迄今未知的机制阻止的。有数据表明，LPC再乙酰化为磷脂酰胆碱（PC）和LPC降解为水溶性甘油酰胆碱（GPC）是一种容量巨大的高效途径。精浆确实提供了巨大的抗氧化潜能，这一事实强调了这一点。因此，我们的建议集中在进一步研究防止不同物种和个体内精子样本中LPC降解的体内机制。我们的目的是调查牛、猪和猫的射精与人类样本的关系，因此前者确实含有醚类脂质。后者的抗氧化潜能迄今为止知之甚少。由于在上一个研究期间所取得的成果，重点不仅需要包括对LPC生成的调查。据信，在生成ROS的过程中，会生成更高分子量的脂质氧化产物（如过氧化物或氯化物）。这些分子量较大的脂质氧化产物的不稳定埃斯特键最有可能被磷脂酶水解，我们正计划对其进行定量研究。再乙酰化和进一步转化为水溶性LPC的最终产物的检测应使用稳定同位素标记的分子（例如13C标记的脂肪酸）进行。这些质谱和核磁共振研究应嵌入到其他方法中，如量热法（测量抗氧化电位），精子膜结构的生物物理测定，以分析病理过程中脂质组成的变化。希望能获得病理过程中脂质组成变化的信息。此外，这些数据将有助于了解这些变化如何在特定物种的水平上影响精子质量。