Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

Haruki Nishizawa, Sayuri Ota, Machiko Suzuki, Takema Kato, Takao Sekiya, Hiroki Kurahashi, Yasuhiro Udagawa

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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.

Original languageEnglish
Article number107
JournalReproductive Biology and Endocrinology
Volume9
DOIs
Publication statusPublished - 02-08-2011

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Gene Expression Profiling
Fetal Development
Pre-Eclampsia
Placenta
Genes
Angiogenesis Inducing Agents
Mothers
Apoptosis
Pregnancy
p53 Genes
Trophoblasts
Caspases
Up-Regulation

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynaecology
  • Developmental Biology

Cite this

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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.",
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Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction. / Nishizawa, Haruki; Ota, Sayuri; Suzuki, Machiko; Kato, Takema; Sekiya, Takao; Kurahashi, Hiroki; Udagawa, Yasuhiro.

In: Reproductive Biology and Endocrinology, Vol. 9, 107, 02.08.2011.

Research output: Contribution to journalArticle

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T1 - Comparative gene expression profiling of placentas from patients with severe pre-eclampsia and unexplained fetal growth restriction

AU - Nishizawa, Haruki

AU - Ota, Sayuri

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AU - Kato, Takema

AU - Sekiya, Takao

AU - Kurahashi, Hiroki

AU - Udagawa, Yasuhiro

PY - 2011/8/2

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