Abstract
BackgroundTrophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs).MethodsThis study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89).ResultsMMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies.ConclusionsHuman placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.
Highlights
Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation
The gelatinases Matrix metalloproteinases (MMPs)-2 and MMP-9 are especially involved in successful cytotrophoblast invasion in early pregnancy as they are considered key enzymes in
The aim of the present study was to compare the serum levels of MMP-9, MMP-2/tissue inhibitors of MMPs (TIMPs)-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89) in order to evaluate the potential roles of matrix-degrading proteases MMP-2 and MMP-9 in the process of early pregnancy failure
Summary
Trophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs). MMPs have the ability to break down several proteins of the extracellular matrix (ECM) and they participate actively in remodeling the ECM by degrading important matrix scaffold macromolecules Together with their tissue inhibitors (TIMPs) they form a balance to maintain normal early pregnancy and placental development. Trophoblasts of the human placenta can differentiate into extravillous trophoblasts (EVT) with invasive properties Proteolytic enzymes such as MMP-2 and MMP-9 are essential for the invasion of EVT cells into endometrial stroma [5]
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