Journal
PLACENTA
Volume 31, Issue 7, Pages 615-620Publisher
W B SAUNDERS CO LTD
DOI: 10.1016/j.placenta.2010.04.003
Keywords
Trophoblast invasion; MMP1; Gene expression; Decidua; Pre-eclampsia; Fetal growth restriction
Funding
- Norwegian University of Science and Technology (NTNU), Trondheim
- Haukeland University Hospital, Bergen, Norway
- Norwegian Microarray Consortium (NTNU)
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Superficial invasion of extravillous trophoblasts (EVTs) and impaired spiral artery remodelling are characterizing phenomena in pregnancies complicated by pre-eclampsia (PE) and fetal growth restriction (FGR). However, the underlying causes remain unclear. In this study, gene expression in decidua basalis tissue from pregnancies complicated with PE and/or FGR (n = 18) and normal pregnancies (n = 17) was assessed by Affymetrix HG Focus microarray to obtain hints of mechanisms involved in the pathogenesis. A total of 200 differentially expressed transcripts were detected at a false discovery rate (FDR) <= 0.1. Several genes involved in trophoblast differentiation and invasion were downregulated, including the matrix metalloproteinases (MMPs) MMP1, -7 and -12. MMPs are a family of enzymes involved in degradation of extracellular matrix and have been ascribed a permissive role in trophoblast invasion. MMP1 had the highest fold change among the differentially expressed genes (four-fold downregulated) and was chosen for further investigation. Reduced MMP1 mRNA in decidual tissue was confirmed by RT-qPCR. MMP1 protein expression in EVTs was assessed by double immunofluorescence analysis, using antibodies against pro-MMP1 and cytokeratin 7. The proportion of MMP1 positive EVTs was reduced in all subgroups of cases (PE: n = 18, FGR: n = 11 and PE + FGR: n = 30) compared to controls (n = 23) (all p's < 0.05). Based on these findings, we hypothesize that reduced levels of MMP1 protein in EVTs could be linked to the impaired trophoblast invasion in PE and/or FGR. (C) 2010 Elsevier Ltd. All rights reserved.
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