CoChat
Sign Up
Cited by 0Sperm and Testicular FunctionGlycosylation and Glycoproteins ResearchReproductive Biology and Fertility

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

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

Open access
Mashiko, Daisuke, Tonai, Shingo, Miyata, Haruhiko, Matzuk, Martin M, Ikawa, Masahito·2025·eLife
DOI 10.7554/elife.107494PMC PMC12611266

Published version of a preprint

Open this paper in CoChat — free account

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.7554/elife.107494

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Flagged first, then by citations

Research works printed but not linked: 54

  1. Aebi, 2013, N-linked protein glycosylation in the ER, Biochimica et Biophysica Acta, 1833, 2430, 10.1016/j.bbamcr.2013.04.001 · DOI
  2. Ahuja, 2019, Structural basis for mammalian nucleotide sugar transport, eLife, 8, 10.7554/eLife.45221 · DOI
  3. Bedford, 1991, Effects of elevated temperature on the epididymis and testis: experimental studies, Advances in Experimental Medicine and Biology, 286, 19, 10.1007/978-1-4684-5913-5_3 · DOI
  4. Bojar, 2022, A useful guide to lectin binding: machine-learning directed annotation of 57 unique lectin specificities, ACS Chemical Biology, 17, 2993, 10.1021/acschembio.1c00689 · DOI
  5. Cheng, 2023, Accurate proteome-wide missense variant effect prediction with AlphaMissense, Science, 381, 10.1126/science.adg7492 · DOI · Paper page
  6. Contreras, 2022, C11orf94/Frey is a key regulator for male fertility by controlling Izumo1 complex assembly, Science Advances, 8, 10.1126/sciadv.abo6049 · DOI
  7. Fujihara, 2012, SPACA1-deficient male mice are infertile with abnormally shaped sperm heads reminiscent of globozoospermia, Development, 139, 3583, 10.1242/dev.081778 · DOI
  8. Fujihara, 2013, Expression of TEX101, regulated by ACE, is essential for the production of fertile mouse spermatozoa, PNAS, 110, 8111, 10.1073/pnas.1222166110 · DOI
  9. Fujihara, 2014, GPI-anchored protein complex, LY6K/TEX101, is required for sperm migration into the oviduct and male fertility in mice, Biology of Reproduction, 90, 60, 10.1095/biolreprod.113.112888 · DOI
  10. Fujihara, 2018, Factors controlling sperm migration through the oviduct revealed by gene-modified mouse models, Experimental Animals, 67, 91, 10.1538/expanim.17-0153 · DOI
  11. Fujihara, 2018, Co-expression of sperm membrane proteins CMTM2A and CMTM2B is essential for ADAM3 localization and male fertility in mice, Journal of Cell Science, 131, 10.1242/jcs.221481 · DOI
  12. Fujihara, 2019, Identification of multiple male reproductive tract-specific proteins that regulate sperm migration through the oviduct in mice, PNAS, 116, 18498, 10.1073/pnas.1908736116 · DOI
  13. Fujihara, 2021, The conserved fertility factor SPACA4/Bouncer has divergent modes of action in vertebrate fertilization, PNAS, 118, 10.1073/pnas.2108777118 · DOI
  14. Hagaman, 1998, Angiotensin-converting enzyme and male fertility, PNAS, 95, 2552, 10.1073/pnas.95.5.2552 · DOI
  15. Hasuwa, 2010, Transgenic mouse sperm that have green acrosome and red mitochondria allow visualization of sperm and their acrosome reaction in vivo, Experimental Animals, 59, 105, 10.1538/expanim.59.105 · DOI
  16. Ikawa, 1997, The putative chaperone calmegin is required for sperm fertility, Nature, 387, 607, 10.1038/42484 · DOI
  17. Inoue, 2005, The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs, Nature, 434, 234, 10.1038/nature03362 · DOI
  18. Inoue, 2008, Putative sperm fusion protein IZUMO and the role of N-glycosylation, Biochemical and Biophysical Research Communications, 377, 910, 10.1016/j.bbrc.2008.10.073 · DOI
  19. Kim, 2006, Mouse sperm lacking ADAM1b/ADAM2 fertilin can fuse with the egg plasma membrane and effect fertilization, The Journal of Biological Chemistry, 281, 5634, 10.1074/jbc.M510558200 · DOI
  20. Kotaja, 2004, Preparation, isolation and characterization of stage-specific spermatogenic cells for cellular and molecular analysis, Nature Methods, 1, 249, 10.1038/nmeth1204-249 · DOI
  21. Krege, 1995, Male-female differences in fertility and blood pressure in ACE-deficient mice, Nature, 375, 146, 10.1038/375146a0 · DOI
  22. Kuhl, 1982, Elliptic Fourier features of a closed contour, Computer Graphics and Image Processing, 18, 236, 10.1016/0146-664X(82)90034-X · DOI
  23. Lin, 2007, Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis, Molecular and Cellular Biology, 27, 6794, 10.1128/MCB.01029-07 · DOI
  24. Lu, 2019, CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice†, Biology of Reproduction, 101, 501, 10.1093/biolre/ioz103 · DOI
  25. Lu, 2023, 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm–egg interaction, PNAS, 120, 10.1073/pnas.2207263120 · DOI
  26. Martinez, 2022, Oligogenic heterozygous inheritance of sperm abnormalities in mouse, eLife, 11, 10.7554/eLife.75373 · DOI
  27. Mashiko, 2017, Mouse spermatozoa with higher fertilization rates have thinner nuclei, PeerJ, 5, 10.7717/peerj.3913 · DOI
  28. Matzuk, 1988, The role of the asparagine-linked oligosaccharides of the alpha subunit in the secretion and assembly of human chorionic gonadotrophin, The Journal of Cell Biology, 106, 1049, 10.1083/jcb.106.4.1049 · DOI
  29. Matzuk, 1989, Site specificity of the chorionic gonadotropin N-linked oligosaccharides in signal transduction, The Journal of Biological Chemistry, 264, 2409, 10.1016/S0021-9258(19)81628-9 · DOI
  30. Miyata, 2015, Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive, Science, 350, 442, 10.1126/science.aad0836 · DOI
  31. Morohoshi, 2021, FAM71F1 binds to RAB2A and RAB2B and is essential for acrosome formation and male fertility in mice, Development, 148, 10.1242/dev.199644 · DOI
  32. Niwa, 1991, Efficient selection for high-expression transfectants with a novel eukaryotic vector, Gene, 108, 193, 10.1016/0378-1119(91)90434-d · DOI
  33. Noda, 2020, Sperm proteins SOF1, TMEM95, and SPACA6 are required for sperm-oocyte fusion in mice, PNAS, 117, 11493, 10.1073/pnas.1922650117 · DOI
  34. Oura, 2022, Genome editing in mice and its application to the study of spermatogenesis, Gene and Genome Editing, 3–4, 10.1016/j.ggedit.2022.100014 · DOI
  35. Pierre, 2012, Absence of Dpy19l2, a new inner nuclear membrane protein, causes globozoospermia in mice by preventing the anchoring of the acrosome to the nucleus, Development, 139, 2955, 10.1242/dev.077982 · DOI
  36. Postma, 2019, PlotsOfData—A web app for visualizing data together with their summaries, PLOS Biology, 17, 10.1371/journal.pbio.3000202 · DOI
  37. Raman, 2012, UDP-N-acetyl-α-D-galactosamine: polypeptide N-acetylgalactosaminyltransferases: completion of the family tree, Glycobiology, 22, 768, 10.1093/glycob/cwv003 · DOI
  38. Robertson, 2020, Large-scale discovery of male reproductive tract-specific genes through analysis of RNA-seq datasets, BMC Biology, 18, 10.1186/s12915-020-00826-z · DOI
  39. Schjoldager, 2020, Global view of human protein glycosylation pathways and functions, Nature Reviews. Molecular Cell Biology, 21, 729, 10.1038/s41580-020-00294-x · DOI
  40. Shamsadin, 1999, Male mice deficient for germ-cell cyritestin are infertile, Biology of Reproduction, 61, 1445, 10.1095/biolreprod61.6.1445 · DOI
  41. Shimada, 2021, ARMC12 regulates spatiotemporal mitochondrial dynamics during spermiogenesis and is required for male fertility, PNAS, 118, 10.1073/pnas.2018355118 · DOI
  42. Takasaki, 2014, A heterozygous mutation of GALNTL5 affects male infertility with impairment of sperm motility, PNAS, 111, 1120, 10.1073/pnas.1310777111 · DOI
  43. Tannous, 2015, N-linked sugar-regulated protein folding and quality control in the ER, 79, 10.1016/j.semcdb.2014.12.001 · DOI
  44. Tiscornia, 2006, Production and purification of lentiviral vectors, Nature Protocols, 1, 241, 10.1038/nprot.2006.37 · DOI
  45. Tokuhiro, 2012, Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility, PNAS, 109, 3850, 10.1073/pnas.1117963109 · DOI
  46. Toshimori, 1992, Masking the cryptodeterminant on the 54-kilodalton mouse sperm surface antigen, Biology of Reproduction, 47, 1161, 10.1095/biolreprod47.6.1161 · DOI
  47. Toyoda, 1971, Studies on the fertilization of mouse eggs in vitro, Jpn. J. Anim. Reprod, 16, 152, 10.1262/jrd1955.16.152 · DOI
  48. Tsirigos, 2015, The TOPCONS web server for consensus prediction of membrane protein topology and signal peptides, Nucleic Acids Research, 43, W401, 10.1093/nar/gkv485 · DOI
  49. Wang, 2020, LYPD4, mouse homolog of a human acrosome protein, is essential for sperm fertilizing ability and male fertility†, Biology of Reproduction, 102, 1033, 10.1093/biolre/ioaa018 · DOI
  50. Wang, 2023, Construction of a cross-species cell landscape at single-cell level, Nucleic Acids Research, 51, 501, 10.1093/nar/gkac633 · DOI
  51. Wang, 2024, Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads, PLOS Genetics, 20, 10.1371/journal.pgen.1011337 · DOI
  52. Yamaguchi, 2006, Aberrant distribution of ADAM3 in sperm from both angiotensin-converting enzyme (Ace)- and calmegin (Clgn)-deficient mice, Biology of Reproduction, 75, 760, 10.1095/biolreprod.106.052977 · DOI
  53. Yamaguchi, 2009, Disruption of ADAM3 impairs the migration of sperm into oviduct in mouse, Biology of Reproduction, 81, 142, 10.1095/biolreprod.108.074021 · DOI
  54. Yao, 2002, Lack of acrosome formation in mice lacking a Golgi protein, GOPC, PNAS, 99, 11211, 10.1073/pnas.162027899 · DOI

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
PMC
PMC12611266
OpenAlex
W4412530404
Cited by
0
References
2
Type
posted content
Language
en
Open access
Licence
Locations
  • eLife (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
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, sperm plasma membrane, zona pellucida binding, oocyte fusion
MeSH terms
Animals, Female, Fertility, Glycoproteins, Infertility, Male, Male, Spermatozoa, Mice, Knockout, Nucleotide Transport Proteins, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review