Glycobiology in Maternal-Fetal Interactions

Glycobiology examines how complex carbohydrates (glycans) and their conjugates modulate communication between mother and developing embryo. At the maternal–fetal interface, glycosylation of proteins and lipids shapes cellular recognition, adhesion and immune tolerance. Trophoblast subtypes—including syncytiotrophoblast, cytotrophoblast and extravillous trophoblast—bear distinct glycan patterns that govern invasion of the decidua, remodelling of uterine vasculature and engagement with maternal immune cells. Glycan‐binding proteins on maternal leucocytes decode these “glyco‐codes”, directing cytokine cascades and angiogenic signalling essential for placental development. Aberrations in N‐glycosylation or fucosylation pathways can impair trophoblast infiltration, provoke inflammatory responses and contribute to pregnancy complications such as pre‐eclampsia, miscarriage and gestational diabetes. Understanding these carbohydrate‐mediated processes offers new biomarkers for pregnancy health and targets for therapeutic intervention.

Research from Nature Portfolio

One seminal study has illuminated the role of pregnancy‐associated plasma protein A (PAPPA) in promoting endometrial receptivity via regulation of N‐fucosylation. The work demonstrated that PAPPA, secreted by trophoblasts, upregulates key fucosyltransferases in endometrial epithelial cells through IGF‐1R/PI3K/Akt signalling. Elevated α1,2‐, α1,3‐ and α1,6‐fucosylation of integrin αVβ3 was shown to enhance blastocyst adhesion and spreading in vitro, while blockade of PAPPA impaired implantation in vivo. This research furnishes a mechanistic link between trophoblast‐derived factors and the dynamic remodelling of the endometrial glycocalyx that underpins successful embryo implantation.

Glycobiology in Maternal-Fetal Interactions publication trend

The graph below shows the total number of articles in glycobiology in maternal-fetal interactions across all publications each year (not limited to Nature Index journals).

Technical terms

Glycosylation: Enzymatic attachment of carbohydrate chains (glycans) to proteins or lipids, affecting structure and function.

N‐glycan: Glycan linked to the amide nitrogen of asparagine residues, forming diverse branched structures critical for cell signalling.

Fucosylation: Addition of fucose monosaccharides to glycan chains, often modulating cell–cell adhesion and immune recognition.

Trophoblast: Placental epithelial cell lineage responsible for embryo implantation, invasion of maternal tissue and nutrient exchange.

Glycan‐binding protein (GBP): Lectin or receptor that recognises specific glycan motifs, transducing signals at the cell surface.

Glycocalyx: Carbohydrate‐rich outer layer on cell membranes, mediating adhesion, shear resistance and intercellular communication.

References

1. Roles of N-linked glycosylation and glycan-binding proteins in placentation: trophoblast infiltration, immunomodulation, angiogenesis, and pathophysiology. Biochemical Society Transactions (2023).
2. Novel function of pregnancy-associated plasma protein A: promotes endometrium receptivity by up-regulating N-fucosylation. Scientific Reports (2017).
3. α1,3-fucosylation of MEST promotes invasion potential of cytotrophoblast cells by activating translation initiation. Cell Death & Disease (2023).
4. Features and Comparative Characteristics of Fucosylated Glycans Expression in Endothelial Glycocalyx of Placental Terminal Villi in Patients with Preeclampsia Treated with Different Antihypertensive Regimens. International Journal of Molecular Sciences (2023).