Project Details
Projekt
Lysophospholipids, species-independent markers of pathological changes of spermatozoa
Subject Area
Reproductive Medicine, Urology
Term
from 2010 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 176888449
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.
DFG Programme
Research Grants
