Insights into embryo-endometrium immune interactions

Embryo implantation requires a tight immune homeostatic control that activates regulatory circuits. One interlocutor is the embryo, which produces soluble ligands and expresses receptors for different autocrine and paracrine factors. The other interlocutor is the receptive endometrium, which produces mediators to regulate proliferation, differentiation, adhesion and invasiveness of the embryo, among other processes. Here, we are going to discuss experimental evidence regarding human embryo-endometrial dialogue and give a new insight of the relevance of the immune cells to coordinate embryo implantation. In this sense, decidualization of endometrial stromal cells is a multistep process that gives rise to mature decidual cells and senescent decidual cells. The first subpopulation secretes pro-implantation factors and begins migration by encapsulating the embryo. In turn, the second does not complete differentiation but rather suffers a process of premature senescence that is characterized by the production of pro-inflammatory factors (SASP, senescence-associated secretory phenotype), which contribute to embryo implantation. However, alterations in these processes or in their regulation through microRNAs lead to the perpetuation of an inflammatory response and alterations in endometrial receptivity. Considering that decidual cells acquire the ability to differentially respond to embryo quality, here we also explored how the soluble factors produced by embryos (classified according to their quality) impact on the inflammatory response and shape dendritic and other immune cell recruitment during the peri implantation period. To address these aspects, we present experimental evidence that links endoplasmic reticulum stress, senescence and inflammation and we discuss whether embryos reprogram the immune response.