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<p>Recurrent pregnancy loss (RPL) remains a devastating outcome for many women, with up to 40–60% of cases classified as unexplained despite extensive clinical workup. During pregnancy, extracellular vesicles (EVs) from the placenta enters into maternal circulation and plays a vital role in completion of a successful pregnancy. Profiling of EVs cargo proteins offers a promising avenue for the pathophysiology of RPL, with the potential to revolutionize diagnosis, prognosis, and treatment strategies. Blood samples were collected from 5 pregnant women with history of RPL and 5 gestational aged-matched healthy pregnant controls. EVs were extracted from plasma and characterized for their size, morphology, number and presence of surface markers. Further, liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis of EV protein was performed to identify differentially expressed proteins (DEPs). In total 508 proteins with unique peptides were identified. Among these 330 proteins were differentially expressed between patients and controls, out of which 94 were significantly expressed (<i>p</i> &lt; 0.05). Based on the expression pattern, 25 proteins were upregulated (log2FC &gt; 1, <i>P</i> &lt; 0.05) and 69 were downregulated. GO enrichment and KEGG pathway enrichment indicated involvement of pathways such as innate immune response, neutrophil degranulation, complement cascade regulation and intrinsic pathway of fibrin clot formation. Protein-protein interaction analysis identified 10 hub proteins (<i>APOH</i>,<i> APOB</i>,<i> APOA1</i>,<i> APOA2</i>,<i> AHSG</i>,<i> TTR</i>,<i> A2M</i>,<i> SERPINC1</i>,<i> ALB</i>,<i> FGB</i>) potentially implicated in RPL pathophysiology. While preliminary, this study provides molecular insights into EV-associated proteins in RPL and highlights potential biomarkers for future validation.</p> Graphical Abstract <p></p>

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Quantitative proteomic profiling of placental extracellular vesicles in recurrent pregnancy loss reveals their role in feto-maternal crosstalk

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Chitra Bhardwaj,
  • Priyanka Srivastava,
  • Ravi Pratap Singh Bhadoriya,
  • Minakshi Rohilla,
  • Anupriya Kaur,
  • Inusha Panigrahi,
  • Seema Chopra

摘要

Recurrent pregnancy loss (RPL) remains a devastating outcome for many women, with up to 40–60% of cases classified as unexplained despite extensive clinical workup. During pregnancy, extracellular vesicles (EVs) from the placenta enters into maternal circulation and plays a vital role in completion of a successful pregnancy. Profiling of EVs cargo proteins offers a promising avenue for the pathophysiology of RPL, with the potential to revolutionize diagnosis, prognosis, and treatment strategies. Blood samples were collected from 5 pregnant women with history of RPL and 5 gestational aged-matched healthy pregnant controls. EVs were extracted from plasma and characterized for their size, morphology, number and presence of surface markers. Further, liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis of EV protein was performed to identify differentially expressed proteins (DEPs). In total 508 proteins with unique peptides were identified. Among these 330 proteins were differentially expressed between patients and controls, out of which 94 were significantly expressed (p < 0.05). Based on the expression pattern, 25 proteins were upregulated (log2FC > 1, P < 0.05) and 69 were downregulated. GO enrichment and KEGG pathway enrichment indicated involvement of pathways such as innate immune response, neutrophil degranulation, complement cascade regulation and intrinsic pathway of fibrin clot formation. Protein-protein interaction analysis identified 10 hub proteins (APOH, APOB, APOA1, APOA2, AHSG, TTR, A2M, SERPINC1, ALB, FGB) potentially implicated in RPL pathophysiology. While preliminary, this study provides molecular insights into EV-associated proteins in RPL and highlights potential biomarkers for future validation.

Graphical Abstract