Date of Award

2010

Degree Type

Thesis

Degree Name

Master of Science

Program

Pharmacology and Toxicology

Supervisor

Dr. Andy V. Babwah

Second Advisor

Dr. A. Watson

Third Advisor

Dr. P. Chidiac

Abstract

During the first trimester of human pregnancy, cytotrophoblasts proliferate within the tips of the chorionic villi to form cell columns that anchor the placenta to the uterus. This migration coincides with a widespread change in the adhesion molecule repertoire of these trophoblasts. Kisspeptin and its receptor, GPR54 are highly expressed in the human placenta and inhibit trophoblast migration in vitro. Here we show that kisspeptin treatment induces increased adhesion of human extravillous trophoblasts to collagen I, suggesting a mechanism of integrin activation. Additionally, inhibition of both protein kinase C and ERK1/2 attenuated this increase, suggesting that these molecules are key positive regulators of trophoblast adhesion. Furthermore, kisspeptin treatment increased blastocyst adhesion to collagen I, suggesting that kisspeptin signaling is a key regulator of trophoblast function during implantation as well as early placentation.

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