Does a lack of sensitivity to the hormone progesterone cause poor adaptation of the uterine lining to pregnancy in advanced age pregnancies?
Advanced age pregnancies (AAPs) are when a pregnant person is 35 years and older. These pregnancies have increased risk of having pregnancy issues including premature birth and miscarriage. AAPs are becoming more common in Canada so understanding what makes these pregnancies higher risk is critical. The endometrium is the inner layer of the uterus. Stromal cells are a highly abundant cell type in the endometrium. Studies have shown that stromal cells change their behavior when exposed to the hormone progesterone. In very early pregnancy, progesterone acts on stromal cells so that they release proteins that act on other cell types. One example is that stromal cells release proteins that cause specific white blood cells to grow in the endometrium. Our lab has data showing that in AAP there are fewer white blood cells in the endometrium. In this project we will examine if fewer white blood cells are in AAP endometrium because of the poor response by stromal cells to progesterone. To do this, we will use stromal cells from both young and AAP donors and treat them with progesterone. This will allow us to identify if there are any differences in the proteins stromal cells make between young and AAP donors. We will then test if endometrial white blood cells behave differently (e.g. grow less), when exposed to proteins made by AAP stromal cells compared to young donor stromal cells. Determining how and why fewer white blood cells exist in AAP endometrium will help us to understand what makes AAPs high risk. This information can help develop future treatments that can counter the risks associated with AAPs and ensure healthy pregnancy outcomes.