The analysis of the ferroptosis metabolic regulatory network in patients with intrauterine adhesions (IUA) using a metabolomics approach

Background : Recently, there has been a notable rise in the prevalence of intrauterine adhesions (IUA), exerting a substantial impact on female reproductive capacity. The phenomenon of ferroptosis is evident in IUA, yet the regulatory network associated with it remains unclear. Consequently, the objective of this study is to elucidate the metabolic regulatory network of ferroptosis in IUA through metabolomics, offering a fresh perspective for a more profound comprehension of the mechanisms underlying IUA. Concurrently, new active metabolites may emerge as potential targets for the prevention and treatment of IUA. Methods and Results : Uterine endometrial samples were collected from both healthy individuals and patients with IUA, with each endometrium pathologically confirmed. Liquid chromatography-mass spectrometry (LC-MS) was employed for sample analysis. A total of 6250 differential metabolites were identified, of which 102 were screened (VIP>1 and P<0.05). Among these, 29 showed upregulation, while 73 were downregulated. KEGG pathway analysis identified biological processes and metabolic pathways. Differentially regulated metabolic pathways included glucose metabolism, amino acid degradation, fatty acid metabolism, etc. Notably associated were pathways like AMPK signaling pathway, unsaturated fatty acid biosynthesis, oxidative phosphorylation, fatty acid biosynthesis, and sphingolipid metabolism. Joint pathway analysis identified six metabolite pathways (Glutathione metabolism, Arachidonic acid metabolism, Citrate cycle (TCA cycle), Lysine degradation, Glycerolipid metabolism, Cysteine and methionine metabolism) from the differentially expressed metabolites (DEMs). These pathways collectively constitute the Ferroptosis metabolic regulatory network in intrauterine adhesions (IUA). Conclusions: This study conducted a non-targeted metabolomics investigation on IUA . Taking the perspective of differential metabolites between normal and IUA, the study utilized metabolomics to reveal the metabolic regulatory network associated with iron death in IUA. ferroptosis in IUA is regulated by multiple metabolic pathways, including lipid metabolism, amino acid metabolism, and energy metabolism. These metabolic pathways, by modulating the activity of key enzymes such as lipid peroxidase and glutathione peroxidase, impact the occurrence and progression of ferroptosis. The metabolic regulatory network of iron death in IUA is closely related to the occurrence of intrauterine adhesions (IUA). ferroptosis plays a crucial role in the pathological process of intrauterine adhesions by regulating the metabolic pathways of adhesive tissues, potentially contributing to the prevention and treatment of IUA. This research not only aids in a deeper understanding of the pathological mechanisms of IUA but also provides new targets and strategies for preventing and treating diseases related to IUA.