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Purpose  Early pregnancy loss (EPL) affects 50–70% pregnant women in first trimester. The precise molecular mechanisms underlying EPL are far from being fully understood. Therefore, we aim to identify the molecular signaling pathways relating to EPL.    Experimental design  We performed proteomics and bioinformatics analysis of the placental villi in women who have undergone EPL and in normal pregnant women. The proteomics data were validated by Western blot analysis.    Results  We identified a total of 5952 proteins in placental villi, of which 588 proteins were differentially expressed in the EPL women. Bioinformatics analysis revealed that these differentially expressed proteins participated in a variety of signaling pathways, including the focal adhesion pathway and ribosome pathway. Moreover, results of the Western blot confirmed that Desmin, Lamin A/C, MMP‐9, and histone H4 were upregulated in EPL and the Lamin C/ Lamin A ratio decreased obviously in EPL. These proteins could be associated with the pathophysiology of EPL. The data have been deposited to the ProteomeXchange with identifier PXD002391.    Conclusion and clinical relevance  Our study demonstrated that the focal adhesion pathway and ribosome pathway are involved in EPL, and these findings might contribute to unveil the pathophysiology of EPL.

Proteomics study reveals that the dysregulation of focal adhesion and ribosome contribute to early pregnancy loss