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<p>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 <i>Galntl5</i>, 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 <i>Adam3</i> or <i>Lypd4</i>, required for ADAM3-dependent and ADAM3-independent pathways, and GALNTL5 binds to <i>N</i>-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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月17日

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  • 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,
  • Masahito Ikawa

摘要

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.