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Semi-Targeted Ultra-High-Performance Chromatography Coupled to Mass Spectrometry Analysis of Phenolic Metabolites in Plasma of Elderly Adults
Published on: April 22, 2022
Plasma metabolomic characterization of premature ovarian insufficiency
Xing-Yu Zhou1, Xin Li1, Jun Zhang1
1Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, No 1838 Guangzhou Northern Road, Guangzhou, 510515, People's Republic of China.
Insights
This study analyzed plasma metabolites in premature ovarian insufficiency (POI) patients, identifying key metabolic changes linked to ovarian reserve. These findings offer potential diagnostic biomarkers for POI.
Area of Science:
- Metabolomics
- Endocrinology
- Reproductive Medicine
Background:
- Premature ovarian insufficiency (POI) is linked to metabolic disturbances affecting lipid and glucose metabolism, potentially leading to long-term complications like cardiovascular disease and osteoporosis.
- The precise metabolic changes underlying POI development and its complications remain poorly understood, with limited characterization of the POI metabolome.
- Understanding these metabolic alterations is crucial for managing POI and its associated health risks.
Purpose of the Study:
- To characterize the plasma metabolome in patients with premature ovarian insufficiency (POI) using untargeted ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) metabolomics.
- To evaluate the relationship between identified plasma metabolic disturbances and ovarian reserve.
- To assess the potential diagnostic value of these metabolic alterations in POI.
Main Methods:
- An observational study involving 30 POI patients and 30 age- and BMI-matched controls.
- Collection of fasting venous blood samples on days 2-4 of the menstrual cycle.
- Untargeted quantitative metabolomic analysis using UHPLC-MS/MS.
Main Results:
- Significant alterations in plasma metabolites were observed in POI patients, with 48 upregulated and 21 downregulated positive metabolites, and 13 upregulated and 48 downregulated negative metabolites.
- Differentially regulated metabolites were implicated in pathways including caffeine metabolism and ubiquinone/terpenoid-quinone biosynthesis.
- Six metabolites, including arachidonoyl amide and 18-HETE, showed strong correlation with ovarian reserve (AUC > 0.8), indicating potential diagnostic biomarker utility.
Conclusions:
- Untargeted UHPLC-MS/MS metabolomics revealed distinct plasma metabolite profiles in POI patients.
- These metabolic differences may contribute to the etiology of POI and its major complications.
- The identified metabolites provide a comprehensive view of POI-associated metabolic changes, offering potential diagnostic and therapeutic insights.
Background:
Premature ovarian insufficiency (POI) patients are predisposed to metabolic disturbances, including in lipid metabolism and glucose metabolism, and metabolic disorders appear to be a prerequisite of the typical long-term complications of POI, such as cardiovascular diseases or osteoporosis. However, the metabolic changes underlying the development of POI and its subsequent complications are incompletely understood, and there are few studies characterizing the disturbed metabolome in POI patients. The aim of this study was to characterize the plasma metabolome in POI by using ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) metabolomics and to evaluate whether these disturbances identified in the plasma metabolome relate to ovarian reserve and have diagnostic value in POI.
Methods:
This observational study recruited 30 POI patients and 30 age- and body mass index (BMI)-matched controls in the Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Nanfang Hospital, Southern Medical University, from January 2018 to October 2020. Fasting venous blood was collected at 9:00 am on days 2-4 of the menstrual cycle and centrifuged for analysis. An untargeted quantitative metabolomic analysis was performed using UHPLC-MS/MS.
Results:
Our study identified 48 upregulated and 21 downregulated positive metabolites, and 13 upregulated and 48 downregulated negative metabolites in the plasma of POI patients. The differentially regulated metabolites were involved in pathways such as caffeine metabolism and ubiquinone and other terpenoid-quinone biosynthesis. Six metabolites with an AUC value > 0.8, including arachidonoyl amide, 3-hydroxy-3-methylbutanoic acid, dihexyl nonanedioate, 18-HETE, cystine, and PG (16:0/18:1), were correlated with ovarian reserve and thus have the potential to be diagnostic biomarkers of POI.
Conclusion:
This UHPLC-MS/MS untargeted metabolomics study revealed differentially expressed metabolites in the plasma of patients with POI. The differential metabolites may not only be involved in the aetiology of POI but also contribute to its major complications. These findings offer a panoramic view of the plasma metabolite changes caused by POI, which may provide useful diagnostic and therapeutic clues for POI disease.

