O-GlcNAcylation in Hyperglycemic Pregnancies: Impact on Placental Function

Front Endocrinol (Lausanne). 2021 Jun 1:12:659733. doi: 10.3389/fendo.2021.659733. eCollection 2021.

Abstract

The dynamic cycling of N-acetylglucosamine, termed as O-GlcNAcylation, is a post-translational modification of proteins and is involved in the regulation of fundamental cellular processes. It is controlled by two essential enzymes, O-GlcNAc transferase and O-GlcNAcase. O-GlcNAcylation serves as a modulator in placental tissue; furthermore, increased levels of protein O-GlcNAcylation have been observed in women with hyperglycemia during pregnancy, which may affect the short-and long-term development of offspring. In this review, we focus on the impact of O-GlcNAcylation on placental functions in hyperglycemia-associated pregnancies. We discuss the following topics: effect of O-GlcNAcylation on placental development and its association with hyperglycemia; maternal-fetal nutrition transport, particularly glucose transport, via the mammalian target of rapamycin and AMP-activated protein kinase pathways; and the two-sided regulatory effect of O-GlcNAcylation on inflammation. As O-GlcNAcylation in the placental tissues of pregnant women with hyperglycemia influences near- and long-term development of offspring, research in this field has significant therapeutic relevance.

Keywords: O-GlNAcase; O-GlcNAc transferase; O-GlcNAcylation; hyperglycemia in pregnancy; placental function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acetylglucosamine / chemistry
  • Acetylglucosamine / metabolism*
  • Female
  • Humans
  • Hyperglycemia / enzymology
  • Hyperglycemia / genetics
  • Hyperglycemia / metabolism*
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism
  • Placenta / enzymology
  • Placenta / metabolism*
  • Pregnancy
  • Pregnancy Complications / genetics
  • Pregnancy Complications / metabolism*
  • Proteins / genetics
  • Proteins / metabolism
  • beta-N-Acetylhexosaminidases / genetics
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Proteins
  • N-Acetylglucosaminyltransferases
  • O-GlcNAc transferase
  • beta-N-Acetylhexosaminidases
  • Acetylglucosamine