Active metabolomics identify potential functional metabolites for preeclampsia prevention.

ABSTRACT

BACKGROUND: Preeclampsia (PE) is a leading cause of maternal and fetal morbidity and mortality, with limited effective clinical treatment options. Active metabolomics offers a promising approach to uncover metabolic changes in PE and identify potential biomarkers or therapeutic targets. This study performed untargeted metabolomics using LC-MS to compare serum samples from preeclampsia and normal pregnancies. METHODS: We performed untargeted metabolomics using liquid chromatography-mass spectrometry (LC-MS) to compare serum samples from PE patients and normal pregnancies. We analyzed the alterations in metabolites and conducted functional experiments to assess the effects of LysoPE(160) on trophoblast cell invasion and migration. Mechanistic studies were performed to explore the potential targeting of GSK-3ß by LysoPE(160). RESULTS: Our metabolomics analysis revealed significant alterations in several metabolites, including lysophosphatidylcholines and organic acids. Notably, LysoPE(160) was found to be downregulated in the serum of PE patients. Functional experiments demonstrated that LysoPE(160) could promote trophoblast cell invasion and migration. Mechanistic studies suggest that the protective effect of LysoPE(160) against PE might be mediated through the modulation of the GSK-3ß/ß-Catenin pathway, with LysoPE(160) potentially targeting the GSK-3ß protein. CONCLUSIONS: Our findings highlight the potential role of LysoPE(160) in the pathophysiology of PE and its ability to modulate the GSK-3ß/ß-Catenin pathway. These results provide new insights into the metabolic changes associated with PE and suggest that LysoPE(160) could serve as a promising biomarker or therapeutic target for the prevention and treatment of PE.