*2.1. Interplay between Immune Cells and PlGF during Pregnancy*

During pregnancy, innate immune cells are the main leukocyte population in the uterus at the time of embryo implantation. Although most studies analyze the role played by a single immune cell type, it is clear that the creation of an adequate microenvironment, supporting the gestation in its various stages, is the result of the reciprocal interaction among mediators and immune cells present during the early stage of pregnancy. In addition to the uNK cells, which are the most abundant and the main protagonists of innate immunity, macrophages and DCs are also present. Importantly, depletion of any of these cell types modifies the uterine environment and hampers the implantation. Changes in the behavior of these cells lead to an imbalance of angiogenic factors and the proinflammatory cytokines and, at the same time, these altered levels of proinflammatory cytokines and angiogenic factors are able to affect the function of immune cells. An altered uterine environment causes defects in trophoblast invasion and placenta damage that trigger a systemic inflammatory response and widespread activation of the endothelium. Thus, the type and function of the immune cells involved in this response are critical and determine whether a viable pregnancy will occur [11,46,126,127].
