Immunity and early pregnancy events: are endocannabinoids the missing link?

The success of pregnancy is dependent on a number of different cell types and signalling pathways, including immune cells which play a vital role in implantation. Immune cells express transcripts for all of the components of the endocannabinoid system, but the role of this system in the function of reproductive tract immune cells is still unclear. In this review, we present the hypothesis that the endocannabinoid signalling system is central to an endocannabinoid-immune-reproductive axis, and that it acts as the link via which immune cells exert their vital influence on implantation and foetal tolerance. Pubmed and Web of Science databases were searched for studies published since 1975 which explore the interaction between the endocannabinoid system and the immune system, the endocannabinoid system in pregnancy as well as the role of immune cells in pregnancy. There is evidence that the endocannabinoid system has established effects in several immune cell lineages including NK cells and T lymphocytes known to be crucial in the development of normal pregnancy. These effects include regulation of cytokine production, chemotaxis and proliferation. The immune system plays a critical role in placental development and foetal tolerance, achieving this through a large number of cytokines and chemokines. We conclude that there are intricate molecular interactions involved in the success of early pregnancy and that the endocannabinoid system, potentially interacting with the immune system, is a key contributor to these events.