Paracrine regulators of implantation

Classical and contemporary studies have shown that endocrine regulation exerted by ovarian hormones priming the endometrium is essential for embryo implantation. Increasing evidence indicates that steroid-induced molecules acting as paracrine modulators are necessary for embryo–uterine interactions. That is the case for calcitonin, heparin-binding epidermal growth factor (EGF)-like growth factor, leukaemia inhibitory factor and other molecules. Furthermore, when the blastocyst enters the uterine cavity, it starts the complex signals that will drive embryo adhesion. The paracrinology of this process is based on the local interplay of molecules, such as the secretion of cytokines that may facilitate the acquisition of endometrial receptivity by controlling the expression of adhesion and anti-adhesion proteins. Finally, during the embryonic invasive phase, uterine stromal–trophoblast dialogue may modulate this self-controlled proteolytic and immunological process to avoid damage to both the embryo and maternal environment.