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Cited by 0Sperm and Testicular FunctionGlycosylation and Glycoproteins ResearchReproductive Biology and Fertility

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SLC35G3 is a UDP-N-acetylglucosamine transporter for sperm glycoprotein formation and underpins male fertility in mice

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Mashiko, Daisuke, Tonai, Shingo, Miyata, Haruhiko, Matzuk, Martin M, Ikawa, Masahito·2025·eLife
DOI 10.7554/elife.107494.3PMC PMC12132321

Preprint — published as 10.7554/elife.107494 · Paper page

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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.

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Metadata

Authors
Mashiko, D., Tonai, S., Miyata, H., Matzuk, M. M., & Ikawa, M.
Affiliations
  • Immunology Frontier Research Center, The University of Osaka (JP)
  • Research Institute for Microbial Diseases, The University of Osaka (JP)
  • Baylor College of Medicine (US)
  • Center for Infectious Disease Education and Research, The University of Osaka (JP)
Corresponding author
Ikawa, Masahito
ORCID
Venue
eLife
Publisher
eLife Sciences Publications, Ltd
Published
2025-11-12
Volume
14
ISSN
2050-084X (ISSN-L)
DOI
10.7554/elife.107494.3
PMC
PMC12132321
OpenAlex
W4410392361
Cited by
0
References
2
FWCI
0.00
Type
journal article
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • Europe PMC (PubMed Central) (submittedVersion, cc-by)
Funders
  • Japan Society for the Promotion of Science (JP21K19569, JP22H03214, JP21H05033, JP22H04922, JP23K20043)
  • Japan Science and Technology Agency (10.52926/jpmjfr211f, 10.52926/jpmjcr21n1)
  • Japan Agency for Medical Research and Development (JP23jf0126001, JP23fa627002, JP23fa627006)
  • Takeda Science Foundation
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD088412)
  • Bill & Melinda Gates Foundation (INV-001902)
  • Osaka University (OU Master Plan Implementation Project)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
Keywords
male fertility, spermatogenesis, round spermatids, zona pellucida binding, oocyte fusion, male infertility

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