Abstract
<title>Abstract</title> <p>Recurrent spontaneous abortion (RSA), defined as the occurrence of two or more consecutive pregnancy losses, has profound implications for women’s physical and mental well-being or familial dynamics. The etiological diversity and multifactorial characteristics of RSA present considerable obstacles to its diagnosis and management. This study utilized a mass spectrometry-based platform to profile metabolites and proteins in RSA patients in comparison to healthy pregnant controls. Differentially expressed molecules were identified and subsequently employed to construct pathways, with the objective of elucidating their associations with the pathogenesis of RSA. A total of 2,250 differentially expressed proteins and 430 differentially abundant metabolites were identified. Pathway enrichment analysis indicated that the proteins were significantly enriched in pathways related to complement and coagulation cascades, extracellular matrix (ECM)-receptor interaction, cell adhesion molecules, and the phospholipase D signaling pathway. Conversely, the metabolites were primarily associated with pathways involving tyrosine metabolism, pyruvate metabolism, and the phospholipase D signaling pathway. Subsequently, we developed a multi-omics correlation network that integrates metabolites and proteins to elucidate their associations with the pathogenesis of RSA. Our analysis identified that the activation of complement/coagulation activation pathways, endothelial-matrix injury, lipid mediator imbalance, neuroendocrine stress, and metabolic exhaustion converge on uteroplacental hypoperfusion, ultimately leading to pregnancy maintenance failure. Further investigation into the key nodes within these pathways may form the basis for the diagnosis and treatment of RSA.</p>