title: Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction.
abstract: BACKGROUND
  It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR.
  
  
  METHODS
  We analyzed differentially expressed genes in placental tissue from severe pre-eclamptic pregnancies (n = 8) and normotensive pregnancies with or (n = 8) without FGR (n = 8) using a microarray method.
  
  
  RESULTS
  A subset of the FGR samples showed a high correlation coefficient overall in the microarray data from the pre-eclampsia samples. Many genes that are known to be up-regulated in pre-eclampsia are also up-regulated in FGR, including the anti-angiogenic factors, FLT1 and ENG, believed to be associated with the onset of maternal symptoms of pre-eclampsia. A total of 62 genes were found to be differentially expressed in both disorders. However, gene set enrichment analysis for these differentially expressed genes further revealed higher expression of TP53-downstream genes in pre-eclampsia compared with FGR. TP53-downstream apoptosis-related genes, such as BCL6 and BAX, were found to be significantly more up-regulated in pre-eclampsia than in FGR, although the caspases are expressed at equivalent levels.
  
  
  CONCLUSIONS
  Our current data indicate a common pathophysiology for FGR and pre-eclampsia, leading to an up-regulation of placental anti-angiogenic factors. However, our findings also suggest that it may possibly be the excretion of these factors into the maternal circulation through the TP53-mediated early-stage apoptosis of trophoblasts that leads to the maternal symptoms of pre-eclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Fujita Health University, Toyoake, Japan. nharuki@fujita-hu.ac.jp
authors.forename: Haruki
authors.initials: H
authors.lastname: Nishizawa
authors.forename: Sayuri
authors.initials: S
authors.lastname: Ota
authors.forename: Machiko
authors.initials: M
authors.lastname: Suzuki
authors.forename: Takema
authors.initials: T
authors.lastname: Kato
authors.forename: Takao
authors.initials: T
authors.lastname: Sekiya
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurahashi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Udagawa
mesh_terms: D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics*; D020869:Gene Expression Profiling; D006801:Humans; D046228:Microarray Analysis; D010920:Placenta / Q000378:metabolism*; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53