Roles of N-linked glycosylation and glycan-binding proteins in placentation: trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology

Abstract

Protein N-linked glycosylation is a structurally diverse post-translational modification that stores biological information in a larger order of magnitude than other post-translational modifications such as phosphorylation, ubiquitination and acetylation. This gives N-glycosylated proteins a diverse range of properties and allows glyco-codes (glycan-related information) to be deciphered by glycan-binding proteins (GBPs). The intervillous space of the placenta is richly populated with membrane-bound and secreted glycoproteins. Evidence exists to suggest that altering the structural nature of their N-glycans can impact several trophoblast functions, which include those related to interactions with decidual cells. This review summarizes trophoblast-related activities influenced by N-glycan–GBP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of N-glycosylated proteins, and how these cells receive decidua-derived signals via N-glycan–GBP interactions. We highlight work on how changes in N-glycosylation relates to the success of trophoblast infiltration, interactions of immunomodulators, and uterine angiogenesis. We also discuss studies that suggest aberrant N-glycosylation of trophoblasts may contribute to the pathogenesis of pregnancy complications (e.g. pre-eclampsia, early spontaneous miscarriages and hydatidiform mole). We propose that a more in-depth understanding of how N-glycosylation shapes trophoblast phenotype during early pregnancy has the potential to improve our approach to predicting, diagnosing and alleviating poor maternal/fetal outcomes associated with placental dysfunction.

Elevated high-mannose N-glycans hamper endometrial decidualization

“… 38 Complex glycan epitopes play essential roles in decidualization, and evidence suggests that altering the structural nature of N-glycans may impact trophoblast function, including those related to interactions with decidual cells. 39 During glycosylation processing, high-mannose is the basis of complex and hybrid N-glycans biosynthesis. Here, we checked the complex glycans by Lectin blot with PHA-E+L.…”

Molecular and Cellular Insights: A Focus on Glycans and the HNK1 Epitope in Autism Spectrum Disorder

“…It also interacts with cytoskeletal regulation and gene expression. Small changes in glycosylation during pregnancy can greatly alter functions essential for a healthy pregnancy and proper neurodevelopment [5]. Glycan epitopes, such as the HNK1 epitope, are also of primary importance in the glutamatergic and GABAergic circuits of parvalbumin neurons in PNNs and are also expressed in extravillous trophoblasts in direct contact with maternal tissue.…”

“…Indeed, glycans and glycan-related proteins are involved in the determination, growth, and regeneration of axons, synaptic activity, myelin formation and glial cells expression. They also have huge functions in the functioning of the placenta, such as trophoblast infiltration, immunomodulation and angiogenesis [5].…”

Normal transferrin glycosylation does not rule out severe ALG1 deficiency

“… 3 , 4 N‐linked glycosylation plays a fundamental role in several biological processes, such as protein folding, 5 endoplasmic reticulum (ER) homeostasis, 6 neuronal function, 7 and placentation. 8 …”