Abstract
Background: The complexity of follicular fluid metabolome presents a huge challenge for qualitative and quantitative metabolite profiling and discovery of the comprehensive biomarkers.
Objective: In order to address this challenge, novel SWATHtoMRM metabolomics method was used for providing broad coverage and excellent quantitative capability to discover the human follicular fluid metabolites related to age and evaluate their relationship with pregnancy outcome and oocyte senescence.
Methods: The patients were divided into four groups according to age, including group A (28 cases, 21- 27 years old), group B (42 cases, 28-34 years old), group C (31 cases, 35-41 years old), and group D (24 cases, 42-48 years old). Follicular fluid samples from 125 IVF patients were analyzed. The differential ions among the four groups were identified by principal components analysis according to accurate mass, isotope ratio, and tandem mass spectroscopic spectra. Then, the differential metabolic pathways were further identified by a KEGG cluster analysis.
Results: A total of 18 metabolites in the follicular fluid differed among the four groups, including amino acids, lipids, hormones, and vitamins. A total of 15 metabolites, including 6-oxohexanoate, phenylalanine, proline, hexadecanoic acid, linoleate, arachidonate, oleic acid, docosahexaenoic acid, LysoPC(16:1), LysoPC(20:5), LysoPC (20:3), 25-hydroxyvitamin D3, 5-dehydroepisterol, 27- hydroxycholesterol, and 5beta-cholestane-3alpha,7alpha,12alpha,23,25-pentol, were down-regulated with age and 3 metabolites, including LysoPC(18:3), LysoPC(18:1), and 13,14-dihydroretinol, were upregulated with age.
Conclusion: Our study provides useful information for revealing the relationship between age and female reproductive capability.
Keywords: Follicular fluid, metabolomics, age, reproductive function, SWATH to MRM, UPLC-QTOF.
Graphical Abstract
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