O-GlcNAc Modification During Pregnancy: Focus on Placental Environment

Abstract

Successful placentation is a key event for fetal development, which commences following embryo implantation into the uterine wall, eliciting decidualization, placentation, and remodeling of blood vessels to provide physiological exchange between embryo-fetus and mother. Several signaling pathways are recruited to modulate such important processes and specific proteins that regulate placental function are a target for the glycosylation with O-linked β-N-acetylglucosamine (O-GlcNAc), or O-GlcNAcylation. This is a reversible post-translational modification on nuclear and cytoplasmic proteins, mainly controlled by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). O-GlcNAcylation has been implicated as a modulator of proteins, both in physiological and pathological conditions and, more recently, O-GlcNAc has also been shown to be an important modulator in placental tissue. In this mini-review, the interplay between O-GlcNAcylation of proteins and placental function will be addressed, discussing the possible implications of this post-translational modification through placental development and pregnancy.

Environmental influences on placental programming and offspring outcomes following maternal immune activation

“…We also observed a sex-specific effect of lower OGT, a marker of cellular stress during pregnancy, in male compared to female placenta; an effect reported previously (Howerton et al, 2013;Howerton & Bale, 2014). The sexual dimorphism of placental OGT expression appears to be influenced by the type of maternal stressor and its magnitude (Lima et al, 2018). Most interestingly, we found OGT to be elevated in female placentas 24 h after exposure to MIA, suggestive of a compensatory protective mechanism which could account for reported female resilience in MIA models.…”

Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation

“…Increased O-GlcNAcylation due to OGA deletion leads to impaired vascularisation at the placental exchange interface, dramatically impacting placental function [ 31 ]. Nutrient and stress sensing through the HBP and O-GlcNAcylation appear to fine-tune placental development [ 32 ]; however, the impact of this pathway during the initial stages of trophoblast development at implantation is unknown. Here, we set out to assess the effects of O-GlcNAcylation on TE and trophoblast function at implantation.…”

O -GlcNAcylation on LATS2 disrupts the Hippo pathway by inhibiting its activity

“…various cellular processes, such as cell growth, mobility, metabolism, and development, by regulating protein stability, localization, activity, and protein-protein interactions (30)(31)(32)(33)(34)(35)(36). In particular, it is well known that O-GlcNAcylation regulates phosphorylationmediated signaling pathways through interplay with phosphorylation (37,38).…”