Background: Diminished ovarian reserve (DOR) refers to the decrease of the number and quality of oocytes in the ovary, which leads to the lack of sex hormones and the decline of fertility in women. DOR can also develop into premature ovarian failure (POF), which affects women's quality of life and is an important cause of female infertility. Oxidative stress is an important cause of fertility decline in DOR patients, which significantly affects follicular microenvironment, oocyte maturation, fertilization and embryo development. Defining specific oxidized lipid components in follicular fluid (FF) of DOR infertile patients can better understand the existing knowledge of intracellular signal transduction.
Methods: UHPLC-MS-MS technology was used to analyze oxylipins metabolic signatures in the FF of DOR patients and females with normal ovarian reserve (NOR) enrolled for the in vitro fertilization (IVF) cycle. The obtained metabolomic profiles were analyzed using the principal component analysis (PCA) and orthogonal projections to latent structure discriminant analysis (OPLS-DA). The Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst databases were used for pathway enrichment analysis.
Results: Fifteen oxylipins were found to be lower in FF of patients with DOR than those in NOR group, including ±20-HDoHE, ±5-iso PGF2α-VI, 12S-HHTrE, 15-deoxy-Δ12,14-PGJ2, 1a,1b-dihomo PGE2, 1a,1b-dihomo PGF2α, 20-COOH-AA, 20-HETE, 8S,15S-DiHETE, PGA2, PGD2, PGE1, PGF1α, PGF2α, PGJ2. The pathway enrichment analysis revealed that the 15 different oxylipins metabolites were closely related to arachidonic acid metabolic pathway.
Conclusions: Metabolomic analysis of FF indicated that disorders of oxylipins metabolism was closely related to ovarian reserve function. Among these oxylipins metabolites, arachidonic acid metabolism undergoes significant changes that affect the development of oocytes thus causing reduced fertility in DOR patients.
Trial registration: ChiCTR, ChiCTR2000038182,Registered 12 September 2020-Retrospectively registered, http://www.chictr.org.cn/ edit.aspx? pid=61313&htm=4