The intricate cellular details of pregnancy demonstrate the complexity of a developing fetus. In the medical community, pregnancy is considered a host-graft response. Previously, it was thought that the mother undergoes a period of immune suppression with an increased risk of infection. While immune suppression is needed in specific periods of pregnancy, leaders in the field state that the immune system needs to be robust and active.
Immune suppression is associated with illness and cancer, however, the immune system during pregnancy requires tolerance. In this case, the immune system cannot be reactive to cells that are not its own. The ability to allow fetal cells to grow and develop is known as immune tolerance. After conception, embryo implantation requires an inflammatory environment to promote cell growth. Different proteins and cytokines help modulate immunity during pregnancy and protect both mother and child from disease. Immune cell regulation is essential at the maternal-fetal interface, which connects the two. An infection at this site can pose a significant risk to the mother and possibly fatal or developmental risk to the child.
Despite the advancement of medicine, pregnancy loss is, unfortunately, still common. Additionally, there are limited therapies to promote the success of early pregnancies. In the past decade, researchers have discovered that specialized immune cells are necessary to prepare the embryo implantation site. These cells, known as T-regulatory (Treg) cells, regulate the immune response in different ways. Tregs specifically protect bacteria that help improve immune function, suppress immune responses to limit chronic inflammation, prevent the body from attacking its own cells, and maintain immune tolerance. As a result, these cells are critical in early pregnancy and necessary for successful embryo implantation. Scientists are currently investigating ways to improve Treg function to promote success in early pregnancy.
A recent paper in The American Journal of Pathology by Dr. Sarah Robertson and others demonstrated that boosting Tregs improves the success of a healthy pregnancy. Robertson is a professor at the School of Biomedicine and a Health and Medical Sciences faculty member at the University of Adelaide, Australia. Her research focuses on mammalian reproduction and development. Specifically, she investigates immune regulation during pregnancy and works to understand the basic principles behind conception, embryo implantation, and fetus development.
Previous work has shown that women who experienced early pregnancy loss have low Treg cell levels and dysregulated Treg function. As a result, the site of embryo implantation could not properly occur. Robertson and others believe Treg cells are an optimal target to improve the success of early pregnancy. The team employed mouse models to test the response of Tregs after exposure to a protein known as interleukin 2 (IL-2). These models were representative of women at significant risk of early pregnancy loss. The team administered IL-2 between conception and embryo implantation to early pregnancy loss at-risk mice. Interestingly, researchers observed improved function of Tregs and significant improvement of successful pregnancies. Additionally, they found fewer immune cells that would target and harm the embryo.
These results demonstrate that IL-2 therapy significantly affects Treg function and can enhance the success rate of early pregnancy. Overall, this research proposes potential therapeutic interventions for women at risk of early pregnancy loss, including women undergoing in vitro fertilization (IVF).
Paper, The American Journal of Pathology, Sarah Robertson, University of Adelaide
