Wnt/Notch Signaling in Trophoblast Development and Preeclampsia
Summary
The Wnt and Notch pathways orchestrate trophoblast proliferation, differentiation and invasion during placental formation. Canonical Wnt signalling via β-catenin supports cytotrophoblast expansion and promotes transition to extravillous trophoblasts, facilitating spiral artery remodelling. Concurrently, Notch receptors interpret cell–cell signals that guide trophoblast fate decisions and regulate invasive behaviour. Dysregulation of these pathways leads to shallow invasion, impaired vascular adaptation and maternal endothelial dysfunction characteristic of preeclampsia. Aberrant expression of ligands such as DLL and JAGGED, altered receptor activation and epigenetic modifications of pathway inhibitors converge to disrupt placental vascularisation and trigger the systemic maternal syndrome. Emerging studies link microRNAs, growth factors and inflammatory mediators to the fine-tuning of Wnt/Notch crosstalk, underscoring potential targets for early diagnosis and intervention.
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Wnt/Notch Signaling in Trophoblast Development and Preeclampsia publication trend
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Technical terms
Wnt signalling: A pathway initiated by secreted glycoproteins that regulate β-catenin stability to control gene transcription governing cell proliferation and differentiation.
Notch signalling: A cell–cell communication mechanism in which membrane-bound receptors engage ligands on adjacent cells to drive gene expression essential for fate determination and invasive behaviour.
Trophoblast: Placental epithelial cells that differentiate into various subtypes, including invasive extravillous trophoblasts and syncytiotrophoblasts, to establish nutrient and gas exchange.
Extravillous trophoblast (EVT): A specialised trophoblast lineage that invades maternal decidua and remodels uterine spiral arteries to ensure adequate blood flow.
Preeclampsia: A pregnancy disorder characterised by new-onset hypertension and systemic maternal endothelial dysfunction often linked to shallow trophoblast invasion and placental hypoxia.
References
- Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling. Frontiers in Genetics (2013).
- Differential expression of beta-catenin and dickkopf-1 in the third trimester placentas from normal and preeclamptic pregnancies: a comparative study. Reproductive Biology and Endocrinology (2013).
- miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia. Biological Research (2021).
- Decoding the molecular pathways governing trophoblast migration and placental development; a literature review. Frontiers in Endocrinology (2024).
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