Reproductive immunology. Modulation of immune responses in pregnancy and effects on pregnancy outcome

PhD ceremony: Mr. J.R. Prins, 14.30 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Reproductive immunology. Modulation of immune responses in pregnancy and effects on pregnancy outcome

Promotor(s): prof. J.G. Aarnoudse, prof. A.J.M. van Oosterhout, prof. S.A. Robertson

Faculty: Medical Sciences

Pregnancy is a unique immunological challenge in which an antigenically distinct fetus and placenta develop in the uterus of the mother. The complex mechanisms by which the fetus avoids rejection, despite expression of paternal antigens, still remain incompletely understood. Disturbances in maternal tolerance are implicated in infertility and reproductive pathologies. For most of these complications no cure has been found yet.

This thesis describes the role of several maternal immune cells and examines the influence of endogenous factors, such as cytokines, and exogenous factors, such as exposure to cigarette smoke and semen on the maternal immune system during pregnancy. Immune parameters were analysed in healthy and complicated pregnancies in both humans and mouse models.

Research showed that during pregnancy, the maternal immune system is regulated through different pathways to guarantee successful pregnancy outcome. Furthermore, the absence or failure of one of these mechanisms leads to a compensatory response of one of the other tolerance mechanisms which is probably necessary to guarantee a successful pregnancy outcome. Our work provides evidence for immunological changes in early pregnancy which lead to later complications. We suggest that during pregnancy several maternal factors, including endocrinal, immunological and environmental ones, will together influence the pregnancy outcome. The results generated in this thesis may provide clues for therapeutic strategies to strengthen immune tolerance in preparation for healthy pregnancy.