Back to Search Start Over

Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation

Authors :
John D. Aplin
Daniel R Brison
Peter T Ruane
Cheryl M J Tan
Melissa Westwood
Daman J. Adlam
Susan J. Kimber
Source :
Ruane, P, Tan, C M J, Adlam, D, Kimber, S, Brison, D R, Aplin, J & Westwood, M 2020, ' Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation ', Cells . https://doi.org/10.3390/cells9102246, Cells, Vol 9, Iss 2246, p 2246 (2020), Cells, Volume 9, Issue 10
Publication Year :
2020

Abstract

Embryo implantation begins with blastocyst trophectoderm (TE) attachment to the endometrial epithelium, followed by the breaching of this barrier by TE-derived trophoblast. Dynamic protein modification with O-linked &beta<br />N-acetylglucosamine (O-GlcNAcylation) is mediated by O-GlcNAc transferase and O-GlcNAcase (OGA), and couples cellular metabolism to stress adaptation. O-GlcNAcylation is essential for blastocyst formation, but whether there is a role for this system at implantation remains unexplored. Here, we used OGA inhibitor thiamet g (TMG) to induce raised levels of O-GlcNAcylation in mouse blastocysts and human trophoblast cells. In an in vitro embryo implantation model, TMG promoted mouse blastocyst breaching of the endometrial epithelium. TMG reduced expression of TE transcription factors Cdx2, Gata2 and Gata3, suggesting that O-GlcNAcylation stimulated TE differentiation to invasive trophoblast. TMG upregulated transcription factors OVOL1 and GCM1, and cell fusion gene ERVFRD1, in a cell line model of syncytiotrophoblast differentiation from human TE at implantation. Therefore O-GlcNAcylation is a conserved pathway capable of driving trophoblast differentiation. TE and trophoblast are sensitive to physical, chemical and nutritive stress, which can occur as a consequence of maternal pathophysiology or during assisted reproduction, and may lead to adverse neonatal outcomes and associated adult health risks. Further investigation of how O-GlcNAcylation regulates trophoblast populations arising at implantation is required to understand how peri-implantation stress affects reproductive outcomes.

Details

Language :
English
Database :
OpenAIRE
Journal :
Ruane, P, Tan, C M J, Adlam, D, Kimber, S, Brison, D R, Aplin, J & Westwood, M 2020, ' Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation ', Cells . https://doi.org/10.3390/cells9102246, Cells, Vol 9, Iss 2246, p 2246 (2020), Cells, Volume 9, Issue 10
Accession number :
edsair.doi.dedup.....a2b4476ca558090a16b5c29b1dbd76f5
Full Text :
https://doi.org/10.3390/cells9102246