title: Matrix metalloproteinase 1 in pre-eclampsia and fetal growth restriction: reduced gene expression in decidual tissue and protein expression in extravillous trophoblasts.
abstract: 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) <or= 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.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), Olav Kyrres gate 11, Trondheim, Norway. ingrid.a.lian@ntnu.no
authors.forename: I A
authors.initials: IA
authors.lastname: Lian
authors.forename: J H
authors.initials: JH
authors.lastname: Toft
authors.forename: G D
authors.initials: GD
authors.lastname: Olsen
authors.forename: M
authors.initials: M
authors.lastname: Langaas
authors.forename: L
authors.initials: L
authors.lastname: Bjørge
authors.forename: I P
authors.initials: IP
authors.lastname: Eide
authors.forename: P E
authors.initials: PE
authors.lastname: Børdahl
authors.forename: R
authors.initials: R
authors.lastname: Austgulen
mesh_terms: D003656:Decidua / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000201:enzymology*; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000201:enzymology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism*
chemical_list: D020781:Matrix Metalloproteinase 1