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Extensive shift in placental transcriptome profile in preeclampsia and placental origin of adverse pregnancy outcomes.

Sõber S, Reiman M, Kikas T, Rull K, Inno R, Vaas P, Teesalu P, Marti JM, Mattila P, Laan M - Sci Rep (2015)

Bottom Line: The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes.Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results.The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.

ABSTRACT
One in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors including LRF, SP1 and AP2 were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.

No MeSH data available.


Related in: MedlinePlus

Differential gene expression in cases of preeclampsia (PE), gestational diabetes (GD), cases of small- and large-for-gestational-age newborns (SGA, LGA) compared to normal pregnancy (Normal) based on RNA-Seq profiling of 40 term placental samples (n = 8/group)(a) Venn diagram showing differentially expressed genes in each pathology group supported by stringent statistical significance criteria (DESeq: FDR < 0.1 and DESeq2: FDR < 0.05). (b) Principal component analysis (PCA, the two first components are plotted) and (c) hierarchical clustering based on transformed read counts of 220 differentially expressed genes across pregnancy complications. The gene expression levels were subjected to variance stabilizing transformation in DESeq and standardized by subtracting the mean expression across all samples from its value for a given sample and then dividing by the standard deviation across all the samples. This scaled expression value, denoted as the row Z-score, is plotted in red-blue color scale with red indicating increased expression and blue indicating decreased expression. Hierarchical clustering of genes (rows) and samples (columns) was based on Pearson’s correlation. Hierarchical clustering trees are shown for the analyzed samples (top) and genes (left). For each sample are shown newborn sex (M, male; F, female), delivery by caesarean section (+/–) and gestational age at birth plotted in white-yellow-red color scale (white < 260, red > 290 gestational days). (d) Significantly enriched categories among the significantly differentially expressed genes in PE (n = 215) from gene set enrichment analysis in g:Profiler. Horizontal bars indicate significance. Blue bars represent GO terms, orange bars represent transcription factor binding sites.
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f2: Differential gene expression in cases of preeclampsia (PE), gestational diabetes (GD), cases of small- and large-for-gestational-age newborns (SGA, LGA) compared to normal pregnancy (Normal) based on RNA-Seq profiling of 40 term placental samples (n = 8/group)(a) Venn diagram showing differentially expressed genes in each pathology group supported by stringent statistical significance criteria (DESeq: FDR < 0.1 and DESeq2: FDR < 0.05). (b) Principal component analysis (PCA, the two first components are plotted) and (c) hierarchical clustering based on transformed read counts of 220 differentially expressed genes across pregnancy complications. The gene expression levels were subjected to variance stabilizing transformation in DESeq and standardized by subtracting the mean expression across all samples from its value for a given sample and then dividing by the standard deviation across all the samples. This scaled expression value, denoted as the row Z-score, is plotted in red-blue color scale with red indicating increased expression and blue indicating decreased expression. Hierarchical clustering of genes (rows) and samples (columns) was based on Pearson’s correlation. Hierarchical clustering trees are shown for the analyzed samples (top) and genes (left). For each sample are shown newborn sex (M, male; F, female), delivery by caesarean section (+/–) and gestational age at birth plotted in white-yellow-red color scale (white < 260, red > 290 gestational days). (d) Significantly enriched categories among the significantly differentially expressed genes in PE (n = 215) from gene set enrichment analysis in g:Profiler. Horizontal bars indicate significance. Blue bars represent GO terms, orange bars represent transcription factor binding sites.

Mentions: We addressed differential expression of the term placental transcriptome in maternal late-onset preeclampsia (LO-PE) and gestational diabetes (GD), and affected fetal growth (small- and large- for-gestational age newborns; SGA, LGA) in comparison to normal (NORM) pregnancies (n = 8/group). Among the studied pregnancy complications, PE placentas were distinguished by a major shift in the expression profile of hundreds of genes (Fig. 2a; Supplementary Data S3; Supplementary Table S1). Differential expression of 215 genes matched the significance criteria applied in this study (DESeq: false discovery rate (FDR) < 0.1, DESeq2: FDR < 0.05; Supplementary Table S1; details in Materials and Methods). Notably, 80% (n = 173) of the differentially expressed genes in LO-PE placentas showed significantly lower transcript levels compared to the NORM group (Fig. 2, Supplementary Data S3). The top list contained known loci implicated in placental function and PE, such as the up-regulated LEP and down-regulated


Extensive shift in placental transcriptome profile in preeclampsia and placental origin of adverse pregnancy outcomes.

Sõber S, Reiman M, Kikas T, Rull K, Inno R, Vaas P, Teesalu P, Marti JM, Mattila P, Laan M - Sci Rep (2015)

Differential gene expression in cases of preeclampsia (PE), gestational diabetes (GD), cases of small- and large-for-gestational-age newborns (SGA, LGA) compared to normal pregnancy (Normal) based on RNA-Seq profiling of 40 term placental samples (n = 8/group)(a) Venn diagram showing differentially expressed genes in each pathology group supported by stringent statistical significance criteria (DESeq: FDR < 0.1 and DESeq2: FDR < 0.05). (b) Principal component analysis (PCA, the two first components are plotted) and (c) hierarchical clustering based on transformed read counts of 220 differentially expressed genes across pregnancy complications. The gene expression levels were subjected to variance stabilizing transformation in DESeq and standardized by subtracting the mean expression across all samples from its value for a given sample and then dividing by the standard deviation across all the samples. This scaled expression value, denoted as the row Z-score, is plotted in red-blue color scale with red indicating increased expression and blue indicating decreased expression. Hierarchical clustering of genes (rows) and samples (columns) was based on Pearson’s correlation. Hierarchical clustering trees are shown for the analyzed samples (top) and genes (left). For each sample are shown newborn sex (M, male; F, female), delivery by caesarean section (+/–) and gestational age at birth plotted in white-yellow-red color scale (white < 260, red > 290 gestational days). (d) Significantly enriched categories among the significantly differentially expressed genes in PE (n = 215) from gene set enrichment analysis in g:Profiler. Horizontal bars indicate significance. Blue bars represent GO terms, orange bars represent transcription factor binding sites.
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Related In: Results  -  Collection

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f2: Differential gene expression in cases of preeclampsia (PE), gestational diabetes (GD), cases of small- and large-for-gestational-age newborns (SGA, LGA) compared to normal pregnancy (Normal) based on RNA-Seq profiling of 40 term placental samples (n = 8/group)(a) Venn diagram showing differentially expressed genes in each pathology group supported by stringent statistical significance criteria (DESeq: FDR < 0.1 and DESeq2: FDR < 0.05). (b) Principal component analysis (PCA, the two first components are plotted) and (c) hierarchical clustering based on transformed read counts of 220 differentially expressed genes across pregnancy complications. The gene expression levels were subjected to variance stabilizing transformation in DESeq and standardized by subtracting the mean expression across all samples from its value for a given sample and then dividing by the standard deviation across all the samples. This scaled expression value, denoted as the row Z-score, is plotted in red-blue color scale with red indicating increased expression and blue indicating decreased expression. Hierarchical clustering of genes (rows) and samples (columns) was based on Pearson’s correlation. Hierarchical clustering trees are shown for the analyzed samples (top) and genes (left). For each sample are shown newborn sex (M, male; F, female), delivery by caesarean section (+/–) and gestational age at birth plotted in white-yellow-red color scale (white < 260, red > 290 gestational days). (d) Significantly enriched categories among the significantly differentially expressed genes in PE (n = 215) from gene set enrichment analysis in g:Profiler. Horizontal bars indicate significance. Blue bars represent GO terms, orange bars represent transcription factor binding sites.
Mentions: We addressed differential expression of the term placental transcriptome in maternal late-onset preeclampsia (LO-PE) and gestational diabetes (GD), and affected fetal growth (small- and large- for-gestational age newborns; SGA, LGA) in comparison to normal (NORM) pregnancies (n = 8/group). Among the studied pregnancy complications, PE placentas were distinguished by a major shift in the expression profile of hundreds of genes (Fig. 2a; Supplementary Data S3; Supplementary Table S1). Differential expression of 215 genes matched the significance criteria applied in this study (DESeq: false discovery rate (FDR) < 0.1, DESeq2: FDR < 0.05; Supplementary Table S1; details in Materials and Methods). Notably, 80% (n = 173) of the differentially expressed genes in LO-PE placentas showed significantly lower transcript levels compared to the NORM group (Fig. 2, Supplementary Data S3). The top list contained known loci implicated in placental function and PE, such as the up-regulated LEP and down-regulated

Bottom Line: The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes.Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results.The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.

View Article: PubMed Central - PubMed

Affiliation: Human Molecular Genetics Research Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia.

ABSTRACT
One in five pregnant women suffer from gestational complications, prevalently driven by placental malfunction. Using RNASeq, we analyzed differential placental gene expression in cases of normal gestation, late-onset preeclampsia (LO-PE), gestational diabetes (GD) and pregnancies ending with the birth of small-for-gestational-age (SGA) or large-for-gestational-age (LGA) newborns (n = 8/group). In all groups, the highest expression was detected for small noncoding RNAs and genes specifically implicated in placental function and hormonal regulation. The transcriptome of LO-PE placentas was clearly distinct, showing statistically significant (after FDR) expressional disturbances for hundreds of genes. Taqman RT-qPCR validation of 45 genes in an extended sample (n = 24/group) provided concordant results. A limited number of transcription factors including LRF, SP1 and AP2 were identified as possible drivers of these changes. Notable differences were detected in differential expression signatures of LO-PE subtypes defined by the presence or absence of intrauterine growth restriction (IUGR). LO-PE with IUGR showed higher correlation with SGA and LO-PE without IUGR with LGA placentas. Whereas changes in placental transcriptome in SGA, LGA and GD cases were less prominent, the overall profiles of expressional disturbances overlapped among pregnancy complications providing support to shared placental responses. The dataset represent a rich catalogue for potential biomarkers and therapeutic targets.

No MeSH data available.


Related in: MedlinePlus