Reproductive Immunology

Research Leader: Professor Sarah Robertson

The Reproductive Immunology group is focused on understanding the immunology and cytokine biology of embryo implantation and establishing healthy pregnancy. In the days after conception the mother's immune system must undergo a transformation to allow the embryo to implant and develop, and failure of maternal immune tolerance to occur is a key reason for infertility and miscarriage.

The group's research shows that immune adaptation in the peri-implantation period not only influences a woman's receptivity to pregnancy, but also impacts pregnancy outcome and health of the baby after birth.

This research seeks to define the sequence of events which generate maternal immune tolerance of the conceptus, including the origin and nature of the biological signals which stimulate immune adaptation to pregnancy. The group has discovered a critical role for the male partner's seminal fluid in conditioning the female reproductive tract for pregnancy. A major focus is to define how seminal fluid causes these changes, and whether some couples experience incompatibility in the seminal fluid signalling pathway.

The group's research tackles the 40% of human infertility attributed to compromised uterine receptivity, since defects in the immune response are thought to underpin this condition, as well as later complications of pregnancy including miscarriage, preeclampsia and preterm delivery. In defining new biological functions for seminal fluid this work also sheds light on forms of male infertility not attributable to conventional sperm parameters. We work in animal models and in humans, and are actively engaged in clinical and commercial translation of our research to develop new treatments for female and male infertility and miscarriage.

Research Priorities:

• What is the mechanism through which immune tolerance is established in early pregnancy to allow the semi-allogeneic embryo to implant and develop?
• Why does this process fail in some women, leading to infertility and miscarriage?
• Do male seminal factors access the uterine cavity after intercourse in women, to influence fertility through promoting endometrial receptivity?
• What is the identity of the male seminal fluid signalling agents, and the mechanism of delivery of male immuneregulatory factors and antigens? What role does sperm RNA deposition into female cells play in this pathway?
• What are the key signals in seminal fluid, or from the conceptus, that drive the maternal T cell response towards Tregmediated tolerance as opposed to Th17- and Th1-mediated rejection, and does insufficiency in these factors contribute to male infertility?
• What is the mechanism through which immune responses activated in the peri-conceptual environment impact later placental development and fetal growth?
• Do different macrophage and dendritic cell phenotypes and their regulators influence reproductive tissue development and function?
• Does exposure to seminal fluid influence female reproductive health through effects on the immune response to sexually transmitted infection, and/or incidence of endometriosis?