Grant: China-Canada Joint Health Research Initiative

Progesterone plays a key role in establishing and maintaining pregnancy, and deficiencies in progesterone's action lead to miscarriage and preterm birth. The reasons for this are not completely understood, but likely involve the immunosuppressive properties of progesterone at the maternal-fetal interface. A plasma protein, known as corticosteroid-binding globulin (CBG), binds steroids like cortisol and progesterone, and regulates their biological activities. This collaborative research project sets out to: (A) determine whether abnormalities in CBG production and/or function influence pregnancy outcomes in Canadian and Chinese women, and (B) define how CBG controls progesterone action at the maternal-fetal interface. It builds on the discovery of a CBG variant, found in many Chinese women, which is not produced adequately and seems to be beneficial for pregnancy. The project also builds on data obtained in China and Canada which show that CBG is a target for enzymes that destroy its steroid-binding properties. It sets out to define how the production of these types of enzymes by placental cells might control the levels and activity of CBG at the site of placental attachment to the uterus, and how this influences the way progesterone acts to promote and sustain pregnancy.