The extracellular matrix is a complex network of macromolecules that support the growth and homeostatic development of organisms. By conveying multiple signaling cascades, it impacts on several biological processes and influences the behaviour of numerous cell types. During the endometrial cycle and the key events necessary for a correct embryo implantation and placentation, this bioactive meshwork is substantially modified to favour endometrial receptivity and vascular adaptation, trophoblast cell migration, and immune activation as well. A correct extracellular remodeling is fundamental for the establishment of a physiological pregnancy; indeed, the occurrence of altered matrix modifications associates with gestational disorders such as preeclampsia. In the present review, we will critically evaluate the role of pivotal matrix constituents in regulating the key steps of embryo implantation and placentation, provide up-to-date information concerning their primary mechanisms of action and discuss on their potential as a novel source of biomarkers and therapeutic targets.
