Differences in gene expression dependent on sampling site in placental tissue of fetuses with intrauterine growth restriction

Tzschoppe, Anja; Struwe, Ellen; Dörr, Helmuth G.; Goecke, Tamme W.; Beckmann, Matthias W.; Schild, R. L.; Dötsch, Jörg

doi:10.1016/j.placenta.2009.12.002

Cited by 35 publications

(21 citation statements)

References 28 publications

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“…There is growing evidence that a dysregulation of spiral artery invasion by EVT in the first trimester is a process contributing to the vascular resistance observed in the pregnancy complications preeclampsia and intrauterine growth restriction (IUGR) in late pregnancy [21,22]. In line with this finding, we and others have previously shown that placental CRH expression and CRH in maternal plasma are significantly elevated in IUGR [23-26]. IUGR is further pathophysiologically characterized by a reduction in trophoblastic syncytialisation rate [27], increased leptin [28] and reduced 11β-HSD2 [29] expression.…”

Section: Introductionsupporting

confidence: 66%

Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

Fahlbusch

Ruebner

Volkert

et al. 2012

Reprod Biol Endocrinol

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BackgroundThe placental syncytiotrophoblast is the major source of maternal plasma corticotropin-releasing hormone (CRH) in the second half of pregnancy. Placental CRH exerts multiple functions in the maternal organism: It induces the adrenal secretion of cortisol via the stimulation of adrenocorticotropic hormone, regulates the timing of birth via its actions in the myometrium and inhibits the invasion of extravillous trophoblast cells in vitro. However, the auto- and paracrine actions of CRH on the syncytiotrophoblast itself are unknown. Intrauterine growth restriction (IUGR) is accompanied by an increase in placental CRH, which could be of pathophysiological relevance for the dysregulation in syncytialisation seen in IUGR placentas.MethodsWe aimed to determine the effect of CRH on isolated primary trophoblastic cells in vitro. After CRH stimulation the trophoblast syncytialisation rate was monitored via syncytin-1 gene expression and beta-hCG (beta-human chorionic gonadotropine) ELISA in culture supernatant. The expression of the IUGR marker genes leptin and 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) was measured continuously over a period of 72 h. We hypothesized that CRH might attenuate syncytialisation, induce leptin, and reduce 11beta-HSD2 expression in primary villous trophoblasts, which are known features of IUGR.ResultsCRH did not influence the differentiation of isolated trophoblasts into functional syncytium as determined by beta-hCG secretion, albeit inducing syncytin-1 expression. Following syncytialisation, CRH treatment significantly increased leptin and 11beta-HSD2 expression, as well as leptin secretion into culture supernatant after 48 h.ConclusionThe relevance of CRH for placental physiology is underlined by the present in vitro study. The induction of leptin and 11beta-HSD2 in the syncytiotrophoblast by CRH might promote fetal nutrient supply and placental corticosteroid metabolism in the phase before labour induction.

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Section: Introductionsupporting

confidence: 66%

Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

Fahlbusch

Ruebner

Volkert

et al. 2012

Reprod Biol Endocrinol

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“…Previous studies have documented that genes involved in hypoxia or metabolism-related genes are common to the group of differentially expressed genes in the FGR placenta [31-34]. However, these findings may require careful interpretation, since the expression of these genes is often affected by sampling site bias [35,36]. In addition, although the question of whether pre-eclampsia and FGR share a common etiology is not a long-standing issue, there have been few comparative expression profiles undertaken for these disorders, and the results are not consistent [37,38].…”

Section: Discussionmentioning

confidence: 99%

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

Nishizawa

Ota

Suzuki

et al. 2011

Reprod Biol Endocrinol

123

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BackgroundIt 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.MethodsWe 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.ResultsA 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.ConclusionsOur 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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“…Firstly, the differences in the examined population due to the large heterogeneity and the diversity of the underlying causes of FGR [2] as well as the variety in the gestational age of maternal sampling or placental biopsies. In particular, Tzschoppe et al (2010) showed that differences in the sampling site may contribute to variability in gene expression across the placental disk in placentas from FGR-affected pregnancies. Since these placentas represent diseased tissue and show characteristic hypoxic/ischemic changes, it may result in more dramatic changes in gene expression levels [42].…”

Section: Discussionmentioning

confidence: 99%

“…In particular, Tzschoppe et al (2010) showed that differences in the sampling site may contribute to variability in gene expression across the placental disk in placentas from FGR-affected pregnancies. Since these placentas represent diseased tissue and show characteristic hypoxic/ischemic changes, it may result in more dramatic changes in gene expression levels [42]. Secondly, posttranscriptional and/or posttranslational modifications may affect the measured levels of the hormones/proteins in the circulation, not always corresponding to the placental expression [37,43,44].…”

Section: Discussionmentioning

confidence: 99%

Decreased placental expression of hPGH, IGF-I and IGFBP-1 in pregnancies complicated by fetal growth restriction

Koutsaki

Sifakis

Zaravinos

et al. 2011

Growth Hormone & IGF Research

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Differences in gene expression dependent on sampling site in placental tissue of fetuses with intrauterine growth restriction

Cited by 35 publications

References 28 publications

Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

Corticotropin-releasing hormone stimulates expression of leptin, 11beta-HSD2 and syncytin-1 in primary human trophoblasts

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

Decreased placental expression of hPGH, IGF-I and IGFBP-1 in pregnancies complicated by fetal growth restriction

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