Noda Taichi, Uriu Reika, Mashiko Daisuke, Shinohara Hina, Qu Yongcun, Taira Ayumu, Matzuk Ryan M, Tahala Duri, Nakano Motochika, Araki Kimi, Yu Zhifeng, Zhang Ying, Matzuk Martin M, Ikawa Masahito
Institute of Resource Development and Analysis, Kumamoto University, 2-2-1 Honjo, Chuo-ku, Kumamoto, Japan.
Priority Organization for Innovation and Excellence, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, Japan.
Nat Commun. 2025 Sep 17;16(1):8264. doi: 10.1038/s41467-025-63805-4.
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.
超过20个在雄性生殖道中表达的基因已被确定为精子迁移至子宫输卵管连接部(UTJ)并穿过该部位的关键因素,它们被分为依赖ADAM3和不依赖ADAM3的途径。与此同时,具有UTJ迁移缺陷的精子与透明带(ZP)的结合也受损。在此,我们证明编码一种精子表面蛋白的Galntl5基因敲除会导致精子与UTJ和ZP的结合受损,纯合子雄性具有严重的不育症。在依赖ADAM3和不依赖ADAM3途径所需的缺乏Adam3或Lypd4的精子中,GALNTL5明显消失,并且GALNTL5与分布在UTJ和ZP上的N - 乙酰半乳糖胺(GalNAc)结合。GalNAc的阻断减少了与UTJ和ZP结合的精子数量。因此,我们揭示了GALNTL5是UTJ迁移和精子 - ZP结合的关键因素,并且精子通过GALNTL5与GalNAc的相互作用与UTJ和ZP结合。