Abstract
The complexity of follicular fluid metabolome presents a significant challenge for qualitative and quantitative metabolite profiling, and for discovering the comprehensive biomarkers. In order to address this challenge, a novel SWATHtoMRM metabolomics method was used for providing broad coverage and excellent quantitative capability to discover the human follicular fluid metabolites related to recurrent spontaneous abortion (RSA) after in vitro fertilization and embryo transfer, and to evaluate their relationship with pregnancy outcome. The follicular fluid samples from the spontaneous abortion group (n = 22) and the control group (n = 22) were analyzed using ultra-performance liquid chromatography high-resolution mass spectrometry. A novel, high-coverage, targeted metabolomics method (SWATH to MRM) and a targeted metabolomics method were used to find and validate the differential metabolites between the two groups. A total of 18 follicular fluid metabolites, including amino acids, cholesterol, vitamins, fatty acids, cholic acid, lysophosphatidylcholine and other metabolites, were identified. In the RSA group, 8 metabolites, namely dehydroepiandrosterone, lysoPC(16:0), lysoPC(18:2), lysoPC(18:1), lysoPC(18:0), lysoPC(20:5), lysoPC(20:4), and lysoPC(20:3), were up-regulated, and 10 metabolites, namely phenylalanine, linoleate, oleic acid, docosahexaenoic acid, lithocholic acid, 25-hydroxyvitamin D3, hydroxycholesterol, 13-hydroxy-alpha-tocopherol, leucine, and tryptophan, were down-regulated. These differential metabolites related to RSA may provide a possible diagnostic basis and therapeutic target for RSA, as well as a scientific basis for elucidating the mechanism of RSA.
Highlights
The occurrence rate of spontaneous abortion is approximately 10%, while the occurrence rate of recurrent spontaneous abortion (RSA) is around 5%1
Targeted metabolomics using multiple reaction monitor (MRM) technique was considered to be the gold standard for metabolite quantitation, as it is characterized by high sensitivity, a wide dynamic range, and good reproducibility; it is limited by low metabolite coverage[22]
We identified 18 RSA-associated metabolites, including cholesterol, vitamins, amino acids, fatty acids, cholic acid, and lysophosphatidylcholine, among others, that could provide a scientific basis for explaining the mechanism of RSA
Summary
The occurrence rate of spontaneous abortion is approximately 10%, while the occurrence rate of recurrent spontaneous abortion (RSA) is around 5%1. The causative factors for approximately 50% of RSA are still unknown, with www.nature.com/scientificreports/. A powerful analytical method with high sensitivity, broad coverage, specificity, and a wide dynamic range is required. High-resolution mass spectrometry, such as time-of-flight, was one of the most popular tools for analyzing complex metabolite profiling, including untargeted and targeted metabolomics[19,20]. Untargeted metabolomics using the sequential window acquisition of all theoretical fragment-ion spectra (SWATH) technique has a broad coverage in metabolite measurement but is limited by sensitivity, dynamic range, and reproducibility for complex biological samples[21]. Targeted metabolomics using multiple reaction monitor (MRM) technique was considered to be the gold standard for metabolite quantitation, as it is characterized by high sensitivity, a wide dynamic range, and good reproducibility; it is limited by low metabolite coverage[22]. We identified 18 RSA-associated metabolites, including cholesterol, vitamins, amino acids, fatty acids, cholic acid, and lysophosphatidylcholine, among others, that could provide a scientific basis for explaining the mechanism of RSA
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