Control of MMP-9 expression at the maternal–fetal interface

Cytotrophoblastic cells (CTB) from first trimester placenta form columns of invasive CTB. This invasive behaviour is due to the ability of CTB to secrete matrix metalloproteinases (MMPs) since 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, extra-cellular matrix glycoproteins and cytokines or growth factors. This review is not intended to be an exhaustive catalogue of potential regulators of trophoblastic MMP-9 secretion but is aimed at summarising the most important signalling pathways involved in MMP-9 regulation.