Matrix metalloproteinase 1 in pre-eclampsia and fetal growth restriction: reduced gene expression in decidual tissue and protein expression in extravillous trophoblasts

Placenta. 2010 Jul;31(7):615-20. doi: 10.1016/j.placenta.2010.04.003. Epub 2010 May 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Decidua / metabolism
  • Female
  • Fetal Growth Retardation / enzymology*
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Matrix Metalloproteinase 1 / metabolism*
  • Pre-Eclampsia / enzymology*
  • Pregnancy
  • Trophoblasts / metabolism*

Substances

  • Matrix Metalloproteinase 1