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<p>Recurrent pregnancy loss (RPL) is a prevalent and complex gestational complication with incompletely elucidated pathological mechanisms. This study conducted a comprehensive analysis of single-cell RNA sequencing data from 22 samples (12 RPL patients and 10 controls with normal pregnancies) to investigate the cellular ecology and molecular mechanisms of RPL. Our findings revealed a decreased proportion of trophoblasts and an increased proportion of immune cells in RPL. We identified a subtype of extravillous trophoblasts (EVTs) that may play a crucial role in RPL pathology. Additionally, Hofbauer cells, <i>γδ</i>-T cells, and uterine NK cells exhibited abnormal immune activation in RPL. Our analysis of EVT subclusters revealed significant alterations in angiogenesis and immune-related pathways in secretory EVTs and endovascular-like EVTs. CellChat analysis revealed attenuated VEGF signalling and enhanced inflammatory signalling in RPL, which may contribute to disease onset. These findings may improve disease prediction and facilitate targeted interventions for RPL patients.</p>

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Single-cell transcriptomics reveals abnormal cell-type perturbations and remodelling of communication networks in recurrent pregnancy loss

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月22日

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  • Min Li,
  • Ping Zhao,
  • Hanxu Yang,
  • Chong Liu,
  • Yijing Chu

摘要

Recurrent pregnancy loss (RPL) is a prevalent and complex gestational complication with incompletely elucidated pathological mechanisms. This study conducted a comprehensive analysis of single-cell RNA sequencing data from 22 samples (12 RPL patients and 10 controls with normal pregnancies) to investigate the cellular ecology and molecular mechanisms of RPL. Our findings revealed a decreased proportion of trophoblasts and an increased proportion of immune cells in RPL. We identified a subtype of extravillous trophoblasts (EVTs) that may play a crucial role in RPL pathology. Additionally, Hofbauer cells, γδ-T cells, and uterine NK cells exhibited abnormal immune activation in RPL. Our analysis of EVT subclusters revealed significant alterations in angiogenesis and immune-related pathways in secretory EVTs and endovascular-like EVTs. CellChat analysis revealed attenuated VEGF signalling and enhanced inflammatory signalling in RPL, which may contribute to disease onset. These findings may improve disease prediction and facilitate targeted interventions for RPL patients.