Placental membrane-type metalloproteinases (MT-MMPs): Key players in pregnancy

Abstract

Membrane-type matrix metalloproteinases (MT-MMPs) are a sub-family of zinc-dependent endopeptidases involved in the degradation of the extracellular matrix. Although MT-MMPs have been mainly characterized in tumor biology, they also play a relevant role during pregnancy. Placental MT-MMPs are required for cytotrophoblast migration and invasion of the uterine wall and in the remodeling of the spiral arteries. They are involved in the fusion of cytotrophoblasts to form the syncytiotrophoblast as well as in angiogenesis. All these processes are crucial for establishing and maintaining a successful pregnancy and, thus, MT-MMP activity has to be tightly regulated in time and space. Indeed, a de-regulation of MT-MMP expression has been linked with pregnancy complications such as preeclampsia (PE), fetal growth restriction (FGR), gestational diabetes mellitus (GDM) and was also found in maternal obesity. Here we review what is currently known about MT-MMPs in the placenta, with a focus on their general features, their localization and their involvement in pregnancy disorders.

Keywords: extracellular matrix; fetal growth restriction, MT-MMP; preeclampsia; trophoblast.

Figure 1.

MT-MMP structure. MT-MMPs are anchored to the membrane either via transmembrane domain (MT1-, MT2-, MT3- and MT5-MMP) or via GPI-anchor (MT4- and MT6-MMP). Cyt: cytoplasmic domain; TM: transmembrane domain; GPI: glycophosphatidylinositol; HxD: hemopexin domain; Hin: hinge region; CD: catalytic domain; Pro: pro-domain.

Figure 2.

RT-PCR analysis of MT-MMP expression in primary trophoblasts isolated from first trimester placenta (FT) vs. third trimester placenta (TT). For the housekeeping gene RPL30 24 cycles were used, for all MT-MMP 27 cycles.