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
- Masahito Ikawa
2025-09-17
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.