Programme(s) to which this project applies:
|☑ MPhil/PhD||☒ MRes[Med]||☒ URIS|
After implantation, the decidua undergoes physiological changes to ensure a successful pregnancy. Key to this is the remodeling of maternal decidual spiral arteries during the first 12 weeks of pregnancy. This process causes a remodeling of the artery wall, transforming the muscular maternal arteries into a high-flow, low-resistance vessel capable of providing adequate placental perfusion to sustain the growing fetus. Failure in vascular remodeling gives rise to pregnancy-associated diseases known as preeclampsia (PE). The cause of vascular remodeling dysregulation in PE is unclear, but it is suggested that hormone/endocrine imbalance would be one of the causes.
Glycodelin-A (GdA) is a glycoprotein abundant in the secretory endometrium, decidua, and amniotic fluid. GdA concentration in the deciduas rise in early pregnancy, and peaks between 6-12th weeks of gestation. GdA interacts by its unique carbohydrate side-chains with various cell types in the human feto-maternal interface, particularly the trophoblasts and the immune cells, and modulates their functions and differentiation to permit successful pregnancy. Despite the importance of GdA glycosylation, its regulation is poorly understood. By using an endometrial organoid model, we demonstrated that sex hormones alter the glycosylation pattern, particularly sialylation, of endometrial GdA.
This project hypothesized that hormonal regulation of GdA glycosylation during the menstrual cycle and early placentation is crucial to controlling the vascular remodeling activity of GdA. Aberrant hormonal status in PE is associated with alteration in glycosylation and defective vascular remodeling activity of GdA, which contributes to the pathophysiology of PE. PE is a common human pregnancy complication affecting 2-5% of pregnancies worldwide and is the leading cause of maternal mortality, preterm birth, and consequent neonatal morbidity and mortality. The outcome of this project will provide the first direct evidence that changes in the glycosylation of decidual glycoprotein are associated with the defective vascular remodeling process.
Dr CL Lee, Department of Obstetrics and Gynaecology
My research focuses on the use of stem cell, organoid, and nanotechnology models to study placenta development and obstetrical syndromes; and investigate the functional role of placenta-derived extracellular vesicles as a modulator of feto-maternal immunotolerance.
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