Language

English

Publication Date

9-17-2025

Journal

Nature Communications

DOI

10.1038/s41467-025-63805-4

PMID

40962834

PMCID

PMC12443989

PubMedCentral® Posted Date

9-17-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Male, Zona Pellucida, Animals, Spermatozoa, Female, Acetylgalactosamine, N-Acetylgalactosaminyltransferases, Mice, Mice, Knockout, Fallopian Tubes, Sperm-Ovum Interactions, Sperm Motility, Uterus, Protein Binding, Lectins, Infertility, Male, Polypeptide N-acetylgalactosaminyltransferase, Humans, Membrane Glycoproteins, ADAM Proteins, Developmental biology, Glycobiology, Cell migration

Published Open-Access

yes

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