Human decidua and invasive trophoblasts are rich sources of nearly all human matrix metalloproteinases

Abstract

Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. As for all invasive cell types, the ability of CTB to infiltrate the uterine wall is facilitated by the activity of matrix metalloproteinases (MMPs), which is regulated by tissue inhibitors of MMPs (TIMPs). There is evidence for the expression of several MMPs and TIMPs in decidua. However, published data are limited. Therefore, to set a foundation for future research, we screened a panel of healthy human deciduas obtained during first, second and third trimester of pregnancy in addition to isolated decidual cell populations for the expression of all known human MMPs and TIMPs by RT-PCR, western blot and immunohistochemistry. In the decidual samples, we detected almost all MMPs and all four TIMPs at mRNA level. While the expression of proMMP-3 and active MMP-13 and -23 was down-regulated in the course of pregnancy, the pro forms of MMP-8, -19 and -23, active MMP-9, -10, -12, -15, -16, -26 and -28, and pro- and active MMP-14 increased towards the end of gestation. All MMPs and TIMPs were expressed in uterine natural killer cells, decidual fibroblasts and/or trophoblasts, with the exception of MMP-20 and -25. In summary, a remarkably broad spectrum of MMPs was expressed at the human feto-maternal interface, reflecting the highly invasive and remodelling effect on placenta formation. It can be speculated that expression of MMPs correlates with the invasive potential of CTBs together with a crucial role in activation of labour at term.

The FOS Transcription Factor Family Differentially Controls Trophoblast Migration and Invasion

“…In this report, we studied FOS familymediated control of MMP expression as an illustration of disparate regulation of these genes by individual FOS family members. We focused on MMPs because they are highly linked with cell invasion and tissue remodeling in a variety of biological systems, including extravillous trophoblast cells (63)(64)(65), and several of these proteases contain well characterized AP-1 binding sites within their proximal promoter regions. In this study, we found that MMP1 (collagenase-I), MMP3 (stromelysin-1), and MMP10 (stromelysin-2) were rapidly induced after trophoblast cells were subjected to a wound-based migration assay or plated on Matrigel.…”

Matrix metalloproteinase-9 deficiency phenocopies features of preeclampsia and intrauterine growth restriction

“…MMPs are secreted as inactive proenzymes that are activated when cleaved by extracellular proteinases (8). A remarkably broad spectrum of MMPs and tissue inhibitors of MMPs are expressed at the human fetomaternal interface, specifically by uterine natural killer cells, decidual cells, and trophoblasts (9). Their significance in mediating placental development is bolstered in results of in vitro experiments that used a broad-spectrum pharmacological MMP inhibitor (10).…”

Molecular Cross-Talk at the Feto–Maternal Interface

“…This switch in integrin expression appears to be essential for the invasive phenotype of EVT (Damsky et al 1994). In addition, EVT express a wide range of proteases, both secreted and cell surface associated, dipeptidyl peptidase IV (Sato et al 2002), carboxypeptidase-M (Nishioka et al 2003), matrix metalloproteinases (MMPs) Anacker et al 2011), and the urokinase plasminogen activator (uPA) system . The gelatinases, MMP-2 and MMP-9, appear to be the most important proteases secreted by EVT for their invasive behavior with the ratio of MMP-2 and MMP-9 altering throughout gestation (Shimonovitz et al 1994;Bischof et al 2000) and inhibition of MMP-9 completely inhibiting EVT invasion in vitro (Librach et al 1991).…”