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<p>High levels of sperm DNA fragmentation index (DFI) represent a critical factor in male infertility, with detrimental effects on embryonic development and offspring well-being. However, selecting sperm with low DFI remains a tremendous challenge. Here, we present an organ-level selection strategy capable of isolating spermatozoa with ultra-low DFI, achieving a remarkable reduction to 0.13% compared to 34.57% observed in raw semen. We design and fabricate a female reproductive tract (FRT)-on-a-chip (FRToC) device that mimics the entire physiological microenvironment for in vivo sperm selection, with clinical validation performed using samples from patients. The FRToC selects sperm with ultra-low DFI (mean: 0.71%) from patients with high DFI (mean: 41.93%), while also ensuring superior sperm motility and acrosome integrity. Additionally, trace sperm proteomic and single-cell copy number variants (CNV) analyses revealed that sperm sorted by FRToC exhibited an increased capacity to mitigate oxidative stress, thus resulting in more intact chromosomes. Our organ-scale selection method underscores the potential of the FRToC to select high-quality spermatozoa, offering a promising improvement for assisted reproductive technology (ART).</p><p></p>

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Female reproductive tract-on-a-chip for selecting sperm with ultra-low DNA fragmentation index

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月14日

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  • Jing Dai,
  • Han Shan,
  • Yifan Gu,
  • Mingde Zheng,
  • Li Lou,
  • Pingyuan Xie,
  • Shen Zhang,
  • Zheng Sun,
  • Fei Gong,
  • Guangxiu Lu,
  • Ge Lin,
  • Zeyu Chen

摘要

High levels of sperm DNA fragmentation index (DFI) represent a critical factor in male infertility, with detrimental effects on embryonic development and offspring well-being. However, selecting sperm with low DFI remains a tremendous challenge. Here, we present an organ-level selection strategy capable of isolating spermatozoa with ultra-low DFI, achieving a remarkable reduction to 0.13% compared to 34.57% observed in raw semen. We design and fabricate a female reproductive tract (FRT)-on-a-chip (FRToC) device that mimics the entire physiological microenvironment for in vivo sperm selection, with clinical validation performed using samples from patients. The FRToC selects sperm with ultra-low DFI (mean: 0.71%) from patients with high DFI (mean: 41.93%), while also ensuring superior sperm motility and acrosome integrity. Additionally, trace sperm proteomic and single-cell copy number variants (CNV) analyses revealed that sperm sorted by FRToC exhibited an increased capacity to mitigate oxidative stress, thus resulting in more intact chromosomes. Our organ-scale selection method underscores the potential of the FRToC to select high-quality spermatozoa, offering a promising improvement for assisted reproductive technology (ART).