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

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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 Nglycan- GBP recognition, exploring how different subtypes of trophoblasts actively adapt to characteristics of the decidualized endometrium through cell-specific expression of Nglycosylated 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 indepth 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.

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APA

Huang, Z., Lai, P. F., Cocker, A. T. H., Haslam, S. M., Dell, A., Brady, H. J. M., & Johnson, M. R. (2023, April 1). Roles of N-linked glycosylation and glycan-binding proteins in placentation: Trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology. Biochemical Society Transactions. Portland Press Ltd. https://doi.org/10.1042/BST20221406

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