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<p>Understanding human endometrial dynamics in the establishment of endometrial receptivity remains a challenge, which limits early diagnosis and treatment of endometrial-factor infertility. Here, we decode the endometrial dynamics of fertile women across the window of implantation and characterize the endometrial deficiency in women with recurrent implantation failure. A computational model capable of both temporal prediction and pattern discovery is used to analyze single-cell transcriptomic data from over 220,000 endometrial cells. The time-series atlas highlights a two-stage stromal decidualization process and a gradual transitional process of the luminal epithelial cells across the window of implantation. In addition, a time-varying gene set regulating epithelium receptivity is identified, based on which the recurrent implantation failure endometria are stratified into two classes of deficiencies. Further investigation uncovers a hyper-inflammatory microenvironment for the dysfunctional endometrial epithelial cells of recurrent implantation failure. The holistic characterization of the physiological and pathophysiological window of implantation and a computational tool trained on this temporal atlas provide a platform for future therapeutic developments.</p>

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Time-series single-cell transcriptomic profiling of luteal-phase endometrium uncovers dynamic characteristics and its dysregulation in recurrent implantation failures

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月2日

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  • Dandan Cao,
  • Yijun Liu,
  • Yanfei Cheng,
  • Jue Wang,
  • Bolun Zhang,
  • Yanhui Zhai,
  • Kongfu Zhu,
  • Ye Liu,
  • Ye Shang,
  • Xiao Xiao,
  • Yi Chang,
  • Yin Lau Lee,
  • William Shu Biu Yeung,
  • Yuanhua Huang,
  • Yuanqing Yao

摘要

Understanding human endometrial dynamics in the establishment of endometrial receptivity remains a challenge, which limits early diagnosis and treatment of endometrial-factor infertility. Here, we decode the endometrial dynamics of fertile women across the window of implantation and characterize the endometrial deficiency in women with recurrent implantation failure. A computational model capable of both temporal prediction and pattern discovery is used to analyze single-cell transcriptomic data from over 220,000 endometrial cells. The time-series atlas highlights a two-stage stromal decidualization process and a gradual transitional process of the luminal epithelial cells across the window of implantation. In addition, a time-varying gene set regulating epithelium receptivity is identified, based on which the recurrent implantation failure endometria are stratified into two classes of deficiencies. Further investigation uncovers a hyper-inflammatory microenvironment for the dysfunctional endometrial epithelial cells of recurrent implantation failure. The holistic characterization of the physiological and pathophysiological window of implantation and a computational tool trained on this temporal atlas provide a platform for future therapeutic developments.