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GALNTL5 binds GalNAc and is required for migration through the uterotubal junction and sperm-zona pellucida binding

Author

Listed:
  • Taichi Noda

    (Kumamoto University
    Kumamoto University
    The University of Osaka)

  • Reika Uriu

    (Kumamoto University)

  • Daisuke Mashiko

    (The University of Osaka)

  • Hina Shinohara

    (Kumamoto University)

  • Yongcun Qu

    (Capital University of Physical Education and Sports)

  • Ayumu Taira

    (Kumamoto University)

  • Ryan M. Matzuk

    (Baylor College of Medicine)

  • Duri Tahala

    (Kumamoto University)

  • Motochika Nakano

    (Kumamoto University)

  • Kimi Araki

    (Kumamoto University
    Kumamoto University)

  • Zhifeng Yu

    (Baylor College of Medicine)

  • Ying Zhang

    (Beijing Normal University)

  • Martin M. Matzuk

    (Baylor College of Medicine)

  • Masahito Ikawa

    (The University of Osaka
    The University of Tokyo
    The University of Osaka
    The University of Osaka)

Abstract

More than 20 genes expressed in the male reproductive tract have been identified as essential factors for sperm migration to and through the utero-tubal junction (UTJ), and they are divided into ADAM3-dependent and ADAM3-independent pathways. In parallel, sperm having UTJ migration defects also show impaired binding to the zona pellucida (ZP). Herein, we demonstrate that knockout of Galntl5, encoding a sperm surface protein, causes impaired sperm binding with the UTJ and ZP, and null males have severe infertility. GALNTL5 appreciably disappears in sperm lacking Adam3 or Lypd4, required for ADAM3-dependent and ADAM3-independent pathways, and GALNTL5 binds to N-acetylgalactosamine (GalNAc) distributed on the UTJ and ZP. Blockage of GalNAc decreases the number of sperm binding to the UTJ and ZP. Thus, we unveil that GALNTL5 is a responsible factor for UTJ migration and sperm-ZP binding, and that sperm bind to the UTJ and ZP through interaction of GALNTL5 and GalNAc.

Suggested Citation

  • Taichi Noda & Reika Uriu & Daisuke Mashiko & Hina Shinohara & Yongcun Qu & Ayumu Taira & Ryan M. Matzuk & Duri Tahala & Motochika Nakano & Kimi Araki & Zhifeng Yu & Ying Zhang & Martin M. Matzuk & Mas, 2025. "GALNTL5 binds GalNAc and is required for migration through the uterotubal junction and sperm-zona pellucida binding," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-63805-4
    DOI: 10.1038/s41467-025-63805-4
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