Metabolic Reprogramming in Recurrent Spontaneous Abortion: Key Biomarkers Identification and Diagnostic Model...

Area of Science:

• Reproductive Biology
• Metabolomics
• Immunology

Background:

• Recurrent spontaneous abortion (RSA) presents complex, often unknown causes.
• Metabolic reprogramming is increasingly recognized as a factor in RSA pathogenesis.

Purpose of the Study:

• To investigate metabolic reprogramming in RSA.
• To identify diagnostic biomarkers for RSA.
• To explore immune-metabolic crosstalk in RSA.

Main Methods:

• Integrated bioinformatics analysis of GEO datasets (GSE26787, GSE165004).
• Weighted gene co-expression network analysis (WGCNA) and machine learning (logistic regression, SVM-RFE, LASSO) for biomarker identification.
• In vitro experiments (PCR, Western blot, CCK-8, Transwell assays) to validate SREBF2 function.
• Immune infiltration analysis (ssGSEA, CIBERSORT) and single-cell RNA sequencing (GSE214607).

Main Results:

• Four key genes (SREBF2, PPARG, SQLE, UCP2) related to lipid/cholesterol metabolism were upregulated in RSA.
• SREBF2 overexpression in endometrial stromal cells negatively affected proliferation, decidualization, and trophoblast migration.
• Significant correlations were found between model genes and specific immune cell subsets.
• Single-cell analysis revealed altered immune cell proportions and expression patterns, particularly in macrophages.

Conclusions:

• Metabolic reprogramming, especially lipid metabolism, is critically involved in RSA.
• Identified genes offer potential diagnostic biomarkers for RSA.
• Lipid metabolism alterations may impact decidual function, trophoblast behavior, and immune tolerance in RSA, suggesting therapeutic targets.