Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

The biological sex of a fetus associates with risk of having specific pregnancy disorders. For example, preterm births are more likely if the fetus is male, while the risk of pre-eclampsia is increased if the fetus is female. Moreover, male fetuses fare poorer in pregnancies afflicted by stress (i.e. infection, malnutrition). These observations suggest that the sex of the developing baby interacts with biological processes important in pregnancy. The placenta (a fetal-derived organ being of the same sex as the fetus) is essential in pregnancy for ensuring adequate maternal blood/nutrient delivery to the developing baby. The placenta also plays a central role in modifying the mother's immune response to ensure that the developing baby is tolerated. Importantly, many disorders of pregnancy associate with inadequate placenta function. Placenta function is controlled in part by specialized immune cells residing within the mother's uterus, and abnormal changes in uterine immune cell behavior associate with abnormal placenta function and disorders of pregnancy. However, it is currently unknown if the sex of the placenta or its cells differentially modifies maternal immune cell biology. This proposal aims to examine how placenta cells of either male or female sex differ from eachother with respect to the genes they express in both healthy and unhealthy women. Further, we will investigate if the biological sex of the placenta and its cells affects uterine immune cell function. This research will generate important knowledge with respect to how the sex of the fetus and its tissues interacts with the mother's immune system in pregnancy. These findings will provide critical insight into possible biological processes that are different in pregnancies with a male or female fetus that may help to provide answers as to why the sex of the baby establishes unique pregnancy outcome risks.