During pregnancy, the placenta is important for the exchange of gases and nutrients between mother and child, and for the production of hormones that regulate maternal and fetal physiology. The blastocyst is surrounded by a layer of fetal trophoblasts, which, upon implantation in the endometrium, play a role in placenta development. This process, called placentation, needs regulation of growth of the fetal capillary network and expansion and remodeling of the maternal uterine vasculature by invading trophoblasts. Defective remodeling of the maternal vasculature is associated with pregnancy complications.
In naturally conceived pregnancy, the baby is semi-allogeneic to the mother, and thereby the maternal immune system is exposed to foreign Human Leucocyte Antigens (HLA antigens) of the child. In oocyte donation pregnancy, the fetus is most of the times completely allogeneic to the mother, and thereby the mother’s immune system is even more exposed to foreign antigens compared to a naturally conceived pregnancy (Figure 1). Consequently, oocyte donation pregnancy is associated with a higher risk of complications including pre-eclampsia (severe hypertension in the mother).
At the maternal-fetal interface layers in the placenta, maternal immune cells, including NK cells, myeloid cells (macrophages), and T cells, come into contact with fetal trophoblasts. As trophoblasts are invading into the endometrium of the mother to establish development of the placenta, they need to be immunologically tolerated by the maternal immune cells. Several mechanisms are at play to establish this (Figure 2).
We are interested in the behavior of fetal trophoblasts and maternal immune cells (especially T cells and myeloid cells), in how they interact and influence each other, and in the mechanisms by which the phenotype and function of these cells are modulated. These features are studied in healthy and complicated pregnancies. Since in oocyte donation pregnancy the embryo is completely allogeneic compared to the mother, we investigate the concept whether the maternal immune system needs to adapt even more to accept the fetus.
The research group also investigates maternal and fetal (micro)chimerism in pregnancy, and possible consequences of pregnancy-induced chimerism on transplantation outcome later in life.
There is a strong collaboration between the department of Immunology and the department of Obstetrics and Gynecology within the Leiden University Medical Center. Our group consists of principal investigators, PhD students, technicians, clinical fellows, and bachelor students, who are performing research to address the aims outlined above.