Grant: DRA : Canada Graduate Research Scholarship - Doctoral Program (CGRS D)

Advanced age pregnancies (AAPs) are when a pregnant person is 35 years of age or older. In Canada AAPs are becoming more common and have a higher risk of developing pregnancy complications. During pregnancy, the inner lining of the uterus develops into the decidua. For a healthy pregnancy, the blood vessels in the decidua need to increase and expand in size in a process called angiogenesis. Endothelial cells (EC) lining the vessel respond to factors and are vital for changing vessel size and shape. If this occurs incorrectly, this leads to issues like poor growth of the baby and pregnancy loss. Our lab has data showing that by mid-pregnancy, AAP mice have poor blood vessel adaptation and poorly developed embryos. However, AAP mice also have more angiogenic factors in the blood. We propose that EC in the AAP uterus cannot respond to these factors properly, resulting in poor vessel adaptation and that these defects occur before the embryo implants into the uterus. Our first aim is to compare vessels and angiogenesis between young and AAP mice. We will mate young and aged female mice and collect the uterus 3 (before embryo implantation) or 6 (early pregnancy) days later. We will compare the vessels and EC between young and AAP. We will also look at the amount of angiogenic factors and the activity of angiogenic receptors. Our second aim is to see whether giving AAP mice angiogenic factor Vegfa can improve decidual angiogenesis and pregnancy outcomes. We will inject a virus that encodes Vegfa into the AAP uterus before mating, then collect the uterus 3, 6, and 10 days after mating. At 10 days we will see if embryo outcomes are better in AAP mice with Vegfa. At 3 and 6 days we will assess vessels and angiogenesis as described in aim 1. This project is important for better understanding the blood vessels in the aging uterus and decidua. In the future, this knowledge will be key for developing treatments that decrease the risk of pregnancy complications in AAP patients.