How the uterine blood vessels may contribute to increased risk of pregnancy complications in older pregnant people

Program Type (Grant): Graduate Studentship Award
Applicant Name: Wilson, Bethan
Competition Cycle: 2023-04
Start Date: 2023-09-01
End Date: 2025-08-31
Supervisor Name: Riddell, Meghan
Institutional Sponsor: Medicine & Dentistry-Physiology
Supervisor Faculty / Department: Medicine & Dentistry-Obstetrics & Gynecology
WCHRI Funder: RAHF/SCHF
Total WCHRI Funding Commitment: $36,000.00

25% of all pregnancies in North America are from people over the age of 35 years old. These are advanced age pregnancies and are at an increased risk of pregnancy complications. Unfortunately, we don't fully understand how age increases pregnancy risk. Studies in mice have shown that changes in the uterine lining with age leads to pregnancy complications. The lining of the uterus adapts to pregnancy by getting thicker and forming a pregnancy-specific tissue: the decidua. Proper formation of the decidua is essential for a successful pregnancy. This tissue has numerous blood vessels that change in shape and size to prepare for pregnancy and during early pregnancy. If these changes do not occur, then pregnancy complications or failure occur. Endothelial cells are the cells that line the inside of blood vessels. Endothelial cells have been shown to drive the ageing process in other tissues in the human body. Though it is known that increased age alters the formation of the decidua, whether uterine endothelial cells change their characteristics or function is unknown. I propose that uterine endothelial cell ageing may directly contribute to the increased risk of pregnancy complications. I propose to study the changes of the endothelial cell genes in pre-pregnancy and the first trimester of pregnancy using human tissue samples. I will determine if there are changes in advanced age pregnancy decidual endothelial cells using single-cell RNA sequencing technology that allows for the measurement of genes in individual cells. Ultimately, my work will provide insight into age-related pregnancy risks and could be used for future therapeutic targets to reduce these risks.