Date of Award


Degree Type



Dr. Peeyush K. Lala

Second Advisor

Dr. Alison Allan

Third Advisor

Dr. Lynne-Marie Postovit


The human placenta is a highly invasive tumour-like organ in which fetal-derived trophoblast cells constitute the major cell type. A subpopulation of trophoblast cells, known as extravillous trophoblast, invades the uterine decidua and maternal arteries to establish sufficient fetal-maternal exchange to maintain healthy utero-placental homeostasis. Trophoblast invasion is highly regulated by a variety of factors at the fetal-maternal interface. Decorin is a member of the small leucine-rich proteoglycan family, produced by the decidua, and is a negative regulator of trophoblast invasiveness. I hypothesized that decorin inhibits vascular endothelial growth factor (VEGF)-stimulated endovascular differentiation and migration by interfering with signalling pathways downstream of VEGF Receptor (VEGFR)-2. Using in vitro migration and endothelial-like tube formation assays, I determined that decorin inhibits trophoblast migration and endovascular differentiation by interfering with VEGF-induced p38 and p44/p42 mitogen-activated protein kinase (MAPK) activation. These results have implications for the pathobiology of preeclampsia, a hypo-invasive trophoblast disorder in pregnancy.



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