Proprotein Convertase 6: a Master Regulator for the Development of Endometrial Receptivity and Embryo Implantation

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Implantation of an embryo into the womb (uterus) is a key step for human development, without which the embryo will only be able to develop to a very early stage the blastocyst stage (about 8 days after fertilization). For successful implantation, the uterus has to prepare itself to be receptive; this preparation is crucial as an ill-prepared uterus will reject the embryo. Such implantation failure is a major cause of early pregnancy loss and female infertility; ~30% of pregnancies end in spontaneous abortion. How the uterus becomes receptive is not well understood. Our recent research has identified that proprotein convertase 6 (PC6), an important master switch responsible for activating other proteins, is tightly regulated in the uterus during its preparation for receptivity and critical for implantation. This project will examine how PC6 acts in the human uterus to make it receptive, by identifying the factors that PC6 controls and how this controlling works. We will use a cell culture model with cells isolated from human term placenta. In addition, there is no means of readily testing whether the uterus is receptive owing to the lack of reliable biomarkers. In this study we will determine whether PC6 (and those molecules controlled by PC6) are potential biomarkers for uterine receptivity. This will be achieved by examining uterine biopsies and uterine washings collected from proven fertile volunteers and patients of proven endometrial infertility. This study will greatly enhance our understanding of how a critical molecule, PC6, acts in the uterus for implantation. The results will provide new knowledge regarding uterine preparation for implantation. The study has considerable implication for developing much-needed diagnostic and therapeutic tools for uterine receptivity and infertility.