Language

English

Publication Date

8-26-2025

Journal

bioRxiv

DOI

10.1101/2025.05.12.653469

PMID

40462929

PMCID

PMC12132321

PubMedCentral® Posted Date

8-26-2025

PubMedCentral® Full Text Version

Pre-Print

Abstract

Despite the recognized importance of glycans in biological phenomena, their complex roles in spermatogenesis and sperm function remain unclear. SLC35G3, a 10-transmembrane protein specifically found in early round spermatids, belongs to the sugar-nucleotide transporter family, indicating its involvement in glycan formation. In this study, we found that Slc35g3 knockout male mice were sterile due to impaired sperm functions in uterotubal junction passage, zona pellucida binding, and oocyte fusion. Mouse SLC35G3 has UDP-GlcNAc transporter activity, and its ablation caused abnormal processing of the sperm plasma membrane and acrosome membrane proteins. Reported human SLC35G3 mutations (F267L and T179HfsTer27) diminished the UDP-GlcNAc transporter activity of SLC35G3, implying infertility risks in males carrying these mutations. Our findings unveil the vital roles of SLC35G3 in the glycan formation of sperm membrane proteins critical for sperm fertilizing ability.

Keywords

Zona pellucida binding, Utero tubal junction penetration, Sterility

Published Open-Access

yes

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