Disruption of O-GlcNAc homeostasis during mammalian oocyte meiotic maturation impacts fertilization

Luhan T. Zhou, Raquel Romar, Mary Ellen Pavone, Cristina Soriano-Úbeda, John Zhang, Chad Slawson, Francesca E. Duncan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Meiotic maturation and fertilization are metabolically demanding processes, and thus the mammalian oocyte is highly susceptible to changes in nutrient availability. O-GlcNAcylation—the addition of a single sugar residue (O-linked β-N-acetylglucosamine) on proteins—is a posttranslational modification that acts as a cellular nutrient sensor and likely modulates the function of oocyte proteins. O-GlcNAcylation is mediated by O-GlcNAc transferase (OGT), which adds O-GlcNAc onto proteins, and O-GlcNAcase (OGA), which removes it. Here we investigated O-GlcNAcylation dynamics in bovine and human oocytes during meiosis and determined the developmental sequelae of its perturbation. OGA, OGT, and multiple O-GlcNAcylated proteins were expressed in bovine cumulus oocyte complexes (COCs), and they were localized throughout the gamete but were also enriched at specific subcellular sites. O-GlcNAcylated proteins were concentrated at the nuclear envelope at prophase I, OGA at the cortex throughout meiosis, and OGT at the meiotic spindles. These expression patterns were evolutionarily conserved in human oocytes. To examine O-GlcNAc function, we disrupted O-GlcNAc cycling during meiotic maturation in bovine COCs using Thiamet-G (TMG), a highly selective OGA inhibitor. Although TMG resulted in a dramatic increase in O-GlcNAcylated substrates in both cumulus cells and the oocyte, there was no effect on cumulus expansion or meiotic progression. However, zygote development was significantly compromised following in vitro fertilization of COCs matured in TMG due to the effects on sperm penetration, sperm head decondensation, and pronuclear formation. Thus, proper O-GlcNAc homeostasis during meiotic maturation is important for fertilization and pronuclear stage development.

Original languageEnglish (US)
Pages (from-to)543-557
Number of pages15
JournalMolecular reproduction and development
Issue number5
StatePublished - May 2019


  • O-GlcNAc
  • fertilization
  • mammalian
  • meiotic maturation
  • oocyte

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology
  • Cell Biology


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