Gene expression in chorionic villous samples at 11 weeks of gestation in women who develop preeclampsia later in pregnancy: implications for screening

Farina, Antonio; Morano, Danila; Arcelli, Diego; Sanctis, Paola De; Sekizawa, Akihiko; Purwosunu, Yuditiya; Zucchini, Cinzia; Simonazzi, Giuliana; Okai, Takashi; Rizzo, Nicola

doi:10.1002/pd.2344

Cited by 25 publications

(15 citation statements)

References 48 publications

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“…25 Previous studies have reported that it is possible to assess gene expression differences in first trimester placentae from pregnancies with known outcomes, well before clinical disease symptoms or developmental abnormalities are apparent. [26][27][28][29][30][31][32] The results of this study correlate with our previous findings in which we have demonstrated a significant reduction in placental BGN from human pregnancies complicated by FGR collected at third trimester gestation compared with gestation-matched controls. 18 The results from this study support a temporal relationship between reduced BGN expression and SGA/FGR and, therefore, suggest a causal role for placental BGN in the success of pregnancy outcome.…”

Section: Discussionsupporting

confidence: 81%

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells

Chui

Gunatillake

Brennecke

et al. 2017

ATVB

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Objective— Biglycan (BGN) has reduced expression in placentae from pregnancies complicated by fetal growth restriction (FGR). We used first trimester placental samples from pregnancies with later small for gestational age (SGA) infants as a surrogate for FGR. The functional consequences of reduced BGN and the downstream targets of BGN were determined. Furthermore, the expression of targets was validated in primary placental endothelial cells isolated from FGR or control pregnancies. Approach and Results— BGN expression was determined using real-time polymerase chain reaction in placental tissues collected during chorionic villous sampling performed at 10 to 12 weeks’ gestation from pregnancies that had known clinical outcomes, including SGA. Short-interference RNA reduced BGN expression in telomerase-immortalized microvascular endothelial cells, and the effect on proliferation, angiogenesis, and thrombin generation was determined. An angiogenesis array identified downstream targets of BGN, and their expression in control and FGR primary placental endothelial cells was validated using real-time polymerase chain reaction. Reduced BGN expression was observed in SGA placental tissues. BGN reduction decreased network formation of telomerase-immortalized microvascular endothelial cells but did not affect thrombin generation or cellular proliferation. The array identified target genes, which were further validated: angiopoetin 4 ( ANGPT4 ), platelet-derived growth factor receptor α ( PDGFRA ), tumor necrosis factor superfamily member 15 ( TNFSF15 ), angiogenin ( ANG ), serpin family C member 1 ( SERPIN1 ), angiopoietin 2 ( ANGPT2 ), and CXC motif chemokine 12 ( CXCL12 ) in telomerase-immortalized microvascular endothelial cells and primary placental endothelial cells obtained from control and FGR pregnancies. Conclusions— This study reports a temporal relationship between altered placental BGN expression and subsequent development of SGA. Reduction of BGN in vascular endothelial cells leads to disrupted network formation and alterations in the expression of genes involved in angiogenesis. Therefore, differential expression of these may contribute to aberrant angiogenesis in SGA pregnancies.

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Section: Discussionsupporting

confidence: 81%

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells

Chui

Gunatillake

Brennecke

et al. 2017

ATVB

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“…Preeclampsia-specific altered gene expression has also been reported in chorionic villus samples obtained in early gestation from pre-symptomatic mothers who went on to develop preeclampsia [10], [11]. Furthermore, it has also been shown that alterations in expression patterns are not confined to the placenta and can be observed in circulating maternal white blood cell populations [12].…”

Section: Introductionmentioning

confidence: 90%

Comprehensive Analysis of Preeclampsia-Associated DNA Methylation in the Placenta

et al. 2014

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BackgroundA small number of recent reports have suggested that altered placental DNA methylation may be associated with early onset preeclampsia. It is important that further studies be undertaken to confirm and develop these findings. We therefore undertook a systematic analysis of DNA methylation patterns in placental tissue from 24 women with preeclampsia and 24 with uncomplicated pregnancy outcome.MethodsWe analyzed the DNA methylation status of approximately 27,000 CpG sites in placental tissues in a massively parallel fashion using an oligonucleotide microarray. Follow up analysis of DNA methylation at specific CpG loci was performed using the Epityper MassArray approach and high-throughput bisulfite sequencing.ResultsPreeclampsia-specific DNA methylation changes were identified in placental tissue samples irrespective of gestational age of delivery. In addition, we identified a group of CpG sites within specific gene sequences that were only altered in early onset-preeclampsia (EOPET) although these DNA methylation changes did not correlate with altered mRNA transcription. We found evidence that fetal gender influences DNA methylation at autosomal loci but could find no clear association between DNA methylation and gestational age.ConclusionPreeclampsia is associated with altered placental DNA methylation. Fetal gender should be carefully considered during the design of future studies in which placental DNA is analyzed at the level of DNA methylation. Further large-scale analyses of preeclampsia-associated DNA methylation are necessary.

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“…The sFlt-1/PlGF ratio has been proposed as an index of antiangiogenic activity that reflects alterations in both biomarkers and it is also a better predictor of PE than either measure alone [40]. A recent study utilized chorionic villous samples which were taken from pregnant women at 11 weeks of gestation, to develop an mRNA profile for those who were destined to become preeclamptic [41]. The authors suggested that alterations in IL-8, MMP-9, HLA-G and chemokine (CXC motif) ligand 10 were potentially useful for assessing risk, but that altered expressions of neurokinin B and HLA-C were the most predictive.…”

Section: Recent Developmentsmentioning

confidence: 99%

Role of Biomarkers in Early Detection of Preeclampsia

Kar¹

2014

JCDR

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Gene expression in chorionic villous samples at 11 weeks of gestation in women who develop preeclampsia later in pregnancy: implications for screening

Abstract: CVS show an aberrant gene profile prior to preeclampsia onset that may be predictive of the disease.

Cited by 25 publications

References 48 publications

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells

Expression of Biglycan in First Trimester Chorionic Villous Sampling Placental Samples and Altered Function in Telomerase-Immortalized Microvascular Endothelial Cells

Comprehensive Analysis of Preeclampsia-Associated DNA Methylation in the Placenta

Role of Biomarkers in Early Detection of Preeclampsia

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