Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 3 de 3
Filter
Add more filters










Database
Language
Publication year range
1.
Placenta ; 32(11): 823-9, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21907405

ABSTRACT

OBJECTIVES: Endoplasmic reticulum (ER) stress has been implicated in both pre-eclampsia (PE) and fetal growth restriction (FGR), and is characterised by activation of three signalling branches: 1) PERK-pEIF2α, 2) ATF6 and 3) splicing of XBP1(U) into XBP1(S). To evaluate the contribution of ER stress in the pathogenesis of PE relative to FGR, we compared levels of ER stress markers in decidual tissue from pregnancies complicated by PE and/or FGR. STUDY DESIGN: Whole-genome transcriptional profiling was performed on decidual tissue from women with PE (n = 13), FGR (n = 9), PE+FGR (n = 24) and controls (n = 58), and used for pathway and targeted transcriptional analyses of ER stress markers. The expression and cellular localisation of ER stress markers was assesses by Western blot and immunofluorescence analyses. RESULTS: Increased ER stress was observed in FGR and PE+FGR, including both the PERK-pEIF2α and ATF6 signalling branches, whereas ER stress was less evident in isolated PE. However, these cases demonstrated elevated levels of XBP1(U) protein. ATF6 and XBP1 immunoreactivity was detected in most (>80%) extravillous trophoblasts, decidual cells and macrophages. No difference in the proportion of immunopositive cells or staining pattern was observed between study groups. CONCLUSIONS: Increased PERK-pEIF2α and ATF6 signalling have been associated with decreased cellular proliferation and may contribute to the impaired placental growth characterising pregnancies with FGR and PE+FGR. XBP1(U) has been proposed as a negative regulator of ER stress, and increased levels in PE may reflect a protective mechanism against the detrimental effects of ER stress.


Subject(s)
Decidua/metabolism , Endoplasmic Reticulum Stress/physiology , Fetal Growth Retardation/metabolism , Pre-Eclampsia/metabolism , Adult , Biomarkers/analysis , Biomarkers/metabolism , Case-Control Studies , Decidua/pathology , Endoplasmic Reticulum Stress/genetics , Female , Fetal Growth Retardation/etiology , Fetal Growth Retardation/genetics , Gene Expression Profiling , Humans , Microarray Analysis , Pre-Eclampsia/etiology , Pre-Eclampsia/genetics , Pregnancy , Pregnancy Complications/etiology , Pregnancy Complications/genetics , Pregnancy Complications/metabolism , Pregnancy Complications/pathology , Up-Regulation/genetics , Young Adult
2.
Mol Hum Reprod ; 16(12): 960-8, 2010 Dec.
Article in English | MEDLINE | ID: mdl-20643876

ABSTRACT

Variation in the Storkhead box-1 (STOX1) gene has previously been associated with pre-eclampsia. In this study, we assess candidate single nucleotide polymorphisms (SNPs) in STOX1 in an independent population cohort of pre-eclamptic (n = 1.139) and non-pre-eclamptic (n = 2.269) women (the HUNT2 study). We also compare gene expression levels of STOX1 and its paralogue, Storkhead box-2 (STOX2) in decidual tissue from pregnancies complicated by pre-eclampsia and/or fetal growth restriction (FGR) (n = 40) to expression levels in decidual tissue from uncomplicated pregnancies (n = 59). We cannot confirm association of the candidate SNPs to pre-eclampsia (P > 0.05). For STOX1, no differential gene expression was observed in any of the case groups, whereas STOX2 showed significantly lower expression in deciduas from pregnancies complicated by both pre-eclampsia and FGR as compared with controls (P = 0.01). We further report a strong correlation between transcriptional alterations reported previously in choriocarcinoma cells over expressing STOX1A and alterations observed in decidual tissue of pre-eclamptic women with FGR.


Subject(s)
Carrier Proteins/genetics , Decidua/metabolism , Pre-Eclampsia/metabolism , Adult , Carrier Proteins/metabolism , Carrier Proteins/physiology , Cohort Studies , Female , Fetal Growth Retardation/genetics , Fetal Growth Retardation/metabolism , Gene Expression , Genotype , Humans , Polymorphism, Single Nucleotide , Pre-Eclampsia/genetics , Pregnancy
3.
Placenta ; 31(7): 615-20, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20452670

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)

Subject(s)
Fetal Growth Retardation/enzymology , Matrix Metalloproteinase 1/metabolism , Pre-Eclampsia/enzymology , Trophoblasts/metabolism , Decidua/metabolism , Female , Gene Expression , Gene Expression Profiling , Humans , Pregnancy
SELECTION OF CITATIONS
SEARCH DETAIL
...