Molecular mediators of implantation

Because cytotrophoblastic cells (CTB) from first-trimester placenta form columns of invasive CTB they have been considered as a model for blastocyst implantation. This invasive behaviour is due to the ability of CTB to secret matrix metalloproteinases (MMPs) because tissue inhibitor of MMP (TIMP) inhibits their invasiveness. Although CTB behave like metastatic cells, in vivo they are only transiently invasive (first trimester) and their invasion is normally limited only to the endometrium and to the proximal third of the myometrium. This temporal and spatial regulation of trophoblast invasion is believed to be mediated in an autocrine way by trophoblastic factors and in a paracrine way by uterine factors. Several types of regulators have been investigated: hormones, extracellular matrix (ECM) glycoproteins and cytokines or growth factors. This review is not intended to be an exhaustive catalogue of all the potential regulators but is aimed at describing the mechanism of action of certain factors relevant in trophoblast–endometrial interactions.