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

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 () and Masahito Ikawa ()
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Taichi Noda: Kumamoto University
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
Zhifeng Yu: Baylor College of Medicine
Ying Zhang: Beijing Normal University
Martin M. Matzuk: Baylor College of Medicine
Masahito Ikawa: The University of Osaka

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-63805-4

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