Study On Unexplained Male Sterility Based On Metabolomics

Part I Study on Metabolomics Analysis PlatformMetabolomics plays a key role in system biology, it can reflect the living status of specific organism effectively. Metabolomics information were acquired mainly by various powerful high throuput analysis technology. In this part, we set up an metabolomic analysis method by UPLC-Orbitrap instrument. Both RP C18 and Hilic chromatography system were investigated to be engaged in metabolomic analysis. With the local metabolites library, we performed useful procedure for a faster shift in the need of changing chromatography column, or other specific need for changing charomatography condition. In our result, the method established could get good peak shape, and good precision, many of them showed good linarity in analysis and the method can be used in metabolomics analysis on serum, urine and seminal plasma samples.To investigate the anti-depression effect of citalopram, above mentioned metabolomic analysis were engaged in. A total of 26 metabolites had been considered as the potential biomarkers involved in the development of depression.,24 metabolites showed the trend to normal level which may correlate to the regulation of drug treatment, and specifically,10 of them could be the key metabolites in the pathogenesis of depression and contribute to evaluate the effect of citalopram. These results indicated that citalopram mediated synergistically abnormalities of the metabolic network including tryptophan metabolism, energy metabolism and synthesis of neurotransmitters, which may be helpful to evaluate its effectiveness by a metabolomics approach.In this part, we also established a targeted metabolomics anlysis method methd, which was fit for the analysis of free fatty acids in whole blood. The easy method can monitor 35 free fatty acids with only 25micro litter whole blood. And it was applied in the investagetion of cardiovascular toxicity of carbon disulfide.Part II Study on Unexplained Male Infertility-an Metabolomics ApproachWe used a gas-chromatography-mass spectrometry (GC-MS) based metabolomics approach to obtain the metabolomic profiling, identify seminal plasma biomarkers associated with UMI by a two-stage population study. A robust OPLS-DA model based on these identified metabolites was able to distinguish 82% of the UMI patients from health controls with a specificity of 92%. In this model,44 metabolites were found differentially expressed in UMI subjects. By pathway enrichment, we identified major changed metabolic pathways related to UMI. Our finding provides new perspective for the diagnosis of UMI.In this study,4-hydroxyphenylacetic acid was identified as a key metabolite in differentiating the UMI and controls. And significant dose-response relationship were founded between 4-hydroxyphenylacetic acid concentration and UMI incidence rate. And ROC curve showed that 4-hydroxyphenylacetic is a potential biomarker for diagnosis of UMI.Various amino acids including tryptophan, phenylalanine, glycine, serine, threonine, isoleucine, proline, valine consistently decreased significantly in seminal plasma of UMI, indicating a possible increased consumption of these amino acids.We also found the concentrations of tryptophan, phenylalanine, glycine, serine, threonine, isoleucine, proline and valine all showed positive relationships with sperm counts while the concentration of their deamination product urea was negatively related to sperm concentration.