Research Square · Oct 27, 2026
Metabolic profiling of declining ovarian reserve based on non-targeted metabolomics
By Zhao T, Huang T, Shi H et al.
Objective To explore serum metabolic profiles and identify key pathways and markers associated with disease progression across different clinical stages of premature ovarian insufficiency (POI). Methods Sixty patients with POI were included in this study and divided into four groups (A, B, C, and D) based on their serum follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), and oestradiol levels and FSH/LH ratio (15 patients per group). A healthy control group (15 participants) was also included. Non-targeted metabolomics was performed using UPLC–MS/MS to systematically compare differences in metabolites and metabolic pathways among the groups. Results As the disease progressed, FSH levels increased in a stepwise manner, whereas AMH and sex hormone levels progressively decreased. The metabolic profiles showed stage-specific characteristics: Group A was mainly characterised by impaired mitochondrial energy metabolism and exposure to exogenous substances; Group B exhibited altered sphingolipid and arachidonic acid metabolism; Group C showed a widespread increase in acylcarnitine levels; and Group D exhibited elevated levels of bile acid intermediates and sphingolipid reprogramming. Pathway enrichment analysis identified methionine, vitamin/porphyrin, bile acid/one-carbon, and sphingolipid/serotonin metabolic pathways. Conclusion Different clinical stages of POI have distinct serum metabolic fingerprints. Serum acylcarnitine profiles, sphingolipid metabolites, and bile acid intermediates are potential biomarkers for evaluating POI progression and could provide metabolomic evidence to support clinical staging and stage-specific intervention strategies.