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BackgroundOvarian reserve is an important factor determining female reproductive potential. The number and quality of oocytes in patients with diminished ovarian reserve (DOR) are reduced, and even if in vitro fertilization-embryo transfer (IVF-ET) is used to assist their pregnancy, the clinical pregnancy rate and live birth rate are still low. Infertility caused by reduced ovarian reserve is still one of the most difficult clinical problems in the field of reproduction. Follicular fluid is the microenvironment for oocyte survival, and the metabolic characteristics of follicular fluid can be obtained by metabolomics technology. By analyzing the metabolic status of follicular fluid, we hope to find the metabolic factors that affect the quality of oocytes and find new diagnostic markers to provide clues for early detection and intervention of patients with DOR.MethodsIn this research, 26 infertile women with DOR and 28 volunteers with normal ovarian reserve receiving IVF/ET were recruited, and their follicular fluid samples were collected for a nontargeted metabonomic study. The orthogonal partial least squares discriminant analysis model was used to understand the separation trend of the two groups, KEGG was used to analyze the possible metabolic pathways involved in differential metabolites, and the random forest algorithm was used to establish the diagnostic model.Results12 upregulated and 32 downregulated differential metabolites were detected by metabolic analysis, mainly including amino acids, indoles, nucleosides, organic acids, steroids, phospholipids, fatty acyls, and organic oxygen compounds. Through KEGG analysis, these metabolites were mainly involved in aminoacyl-tRNA biosynthesis, tryptophan metabolism, pantothenate and CoA biosynthesis, and purine metabolism. The AUC value of the diagnostic model based on the top 10 metabolites was 0.9936.ConclusionThe follicular fluid of patients with DOR shows unique metabolic characteristics. These data can provide us with rich biochemical information and a research basis for exploring the pathogenesis of DOR and predicting ovarian reserve function.

Mass spectrometry (MS)-based lipidomic has become a powerful tool for studying lipids in biological systems. However, lipidome analysis at the single-cell level remains a challenge. Here, we report a highly sensitive lipidomic workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry (TIMS)-MS. This approach enables the high-coverage identification of lipidome landscape at the single-oocyte level. By using the proposed method, comprehensive lipid changes in porcine oocytes during their maturation were revealed. The results provide valuable insights into the structural changes of lipid molecules during porcine oocyte maturation, highlighting the significance of sphingolipids and glycerophospholipids. This study offers a new approach to the single-cell lipidomic.

The biological functions of lipids largely depend on their chemical structures. The position of C=C bonds is an essential attribute that determines the structures of unsaturated lipids. Here, we developed a new type of chemical derivatization method for C=C bond using aziridination reaction. This new cyclization method for the C=C bonds in lipids based on the direct N-Me aziridination reaction of olefins using N-methyl-O-tosylhydroxylamine (TsONHCH3) as the aminating reagent. When combined with the tandem MS analysis, this novel activation approach for C=C bonds enables the accurate identification their positions in different kinds of unsaturated lipids. Furthermore, an integrated workflow has been established for comprehensively identifying the C=C bond positional isomers of lipids in complicated biological sample. This work provided a new chemical approach for the structural lipidomics.