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The glycosyltransferase EOGT regulates adropin expression in decidualizing human endometrium
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Muter, Joanne, Alam, Mohammad T., Vrljicak, Pavle, Barros, Flavio S. V., Ruane, Peter T., Ewington, Lauren J., Aplin, John D., Westwood, Melissa and Brosens, Jan J. (2018) The glycosyltransferase EOGT regulates adropin expression in decidualizing human endometrium. Endocrinology, 159 (2). pp. 994-1004. doi:10.1210/en.2017-03064
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Official URL: https://doi.org/10.1210/en.2017-03064
Abstract
In pregnancy, resistance of endometrial decidual cells to stress signals is critical for the integrity of the feto-maternal interface and, by extension, survival of the conceptus. O-GlcNAcylation is an essential post-translational 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-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, OGA). Notably, EOGT, an endoplasmic reticulum-specific O-GlcNAc transferase 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 ENHO, which encodes adropin, a metabolic hormone involved in energy homeostasis and glucose and fatty acid metabolism. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between endometrial EOGT and ENHO expression and body mass index. Taken together, our findings reveal that obesity impairs the EOGT-adropin axis in decidual cells, which in turn points towards a novel mechanistic link between metabolic disorders and adverse pregnancy outcome. [Abstract copyright: Copyright © 2017 Endocrine Society.]
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RG Gynecology and obstetrics |
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| Divisions: | Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Medicine > Warwick Medical School |
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| SWORD Depositor: | Library Publications Router | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Endometrium -- physiological aspects, Miscarriage | ||||||||||||
| Journal or Publication Title: | Endocrinology | ||||||||||||
| Publisher: | Endocrine Society | ||||||||||||
| ISSN: | 0013-7227 | ||||||||||||
| Official Date: | 1 February 2018 | ||||||||||||
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| Date of first compliant deposit: | 17 January 2018 | ||||||||||||
| Volume: | 159 | ||||||||||||
| Number: | 2 | ||||||||||||
| Page Range: | pp. 994-1004 | ||||||||||||
| DOI: | 10.1210/en.2017-03064 | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||||||
| RIOXX Funder/Project Grant: |
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