The glycosyltransferase EOGT regulates adropin expression in decidualizing human endometrium

Joanne Muter, Mohammad T. Alam, Pavle Vrljicak, Flavio S.V. Barros, Peter T. Ruane, Lauren J. Ewington, John D. Aplin, Melissa Westwood, Jan J. Brosens

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the fetomaternal interface and, by extension, survival of the conceptus. O-GlcNAcylation is an essential posttranslational modification that links glucose sensing to cellular stress resistance. Unexpectedly, decidualization of primary endometrial stromal cells (EnSCs) was associated with a 60% reduction in O-linked b-N-acetylglucosamine (O-GlcNAc)‒modified proteins, reflecting downregulation of the enzyme that adds O-GlcNAc to substrates (O-GlcNAc transferase; OGT) but not the enzyme that removes the modification (O-GlcNAcase). Notably, epidermal growth factor domain–specific O-linked GlcNAc transferase (EOGT), an endoplasmic reticulum-specific OGT that modifies a limited number of secreted and membrane proteins, was markedly induced in differentiating EnSCs. Knockdown of EOGT perturbed a network of decidual genes involved in multiple cellular functions. The most downregulated gene upon EOGT knockdown in decidualizing cells was the energy homeostasis–associated gene (ENHO), which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism. Analysis of midluteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index. Taken together, our findings revealed that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points toward a mechanistic link between metabolic disorders and adverse pregnancy outcome.

Original languageEnglish
Pages (from-to)994-1004
Number of pages11
JournalEndocrinology
Volume159
Issue number2
DOIs
Publication statusPublished - Feb 2018
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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