title: Increased endoplasmic reticulum stress in decidual tissue from pregnancies complicated by fetal growth restriction with and without pre-eclampsia.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian, University of Science and Technology (NTNU), Women and Children's Centre, N-7006 Trondheim, Norway. ingrid.alsos.lian@gmail.com
authors: I A
authors: IA
authors: Lian
authors: M
authors: M
authors: Løset
authors: S B
authors: SB
authors: Mundal
authors: M H
authors: MH
authors: Fenstad
authors: M P
authors: MP
authors: Johnson
authors: I P
authors: IP
authors: Eide
authors: L
authors: L
authors: Bjørge
authors: K A
authors: KA
authors: Freed
authors: E K
authors: EK
authors: Moses
authors: R
authors: R
authors: Austgulen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics / Q000502:physiology*; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D011225:Pre-Eclampsia / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers