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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

Top 20 transcripts((a) logarithmic scale) and protein coding genes ((b) linear scale) with the highest expression in placentas representing normal pregnancy (NORM) and cases of preeclampsia (PE), gestational diabetes (GD), small- and large-for-gestational-age newborns (SGA, LGA) (n = 8/group). Annotation of placental transcripts detected and quantified by the RNA-Seq pipeline was based on ENSEMBL v67 database. Gene expression levels are expressed in FPKM (fragments per kilobase of exons per million mapped fragments) as determined by cufflinks v 2.0.2. Data on the enrichment of gene expression in the placenta compared to other tissues was derived from Protein Atlas v12. Expression profile across tissues for noncoding RNAs was not available. Boxed gene names indicate transcripts ranked among the top-20 highest expressed genes only in specific pregnancy complications, comparative expression values of these transcripts in all studied groups are shown in Supplementary Fig. S3.
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f1: Top 20 transcripts((a) logarithmic scale) and protein coding genes ((b) linear scale) with the highest expression in placentas representing normal pregnancy (NORM) and cases of preeclampsia (PE), gestational diabetes (GD), small- and large-for-gestational-age newborns (SGA, LGA) (n = 8/group). Annotation of placental transcripts detected and quantified by the RNA-Seq pipeline was based on ENSEMBL v67 database. Gene expression levels are expressed in FPKM (fragments per kilobase of exons per million mapped fragments) as determined by cufflinks v 2.0.2. Data on the enrichment of gene expression in the placenta compared to other tissues was derived from Protein Atlas v12. Expression profile across tissues for noncoding RNAs was not available. Boxed gene names indicate transcripts ranked among the top-20 highest expressed genes only in specific pregnancy complications, comparative expression values of these transcripts in all studied groups are shown in Supplementary Fig. S3.

Mentions: We ordered the genes by their median expression level, ranging from 0 to 40,923 FPKM (fragments per kilobase of exons per million mapped fragments) in placentas from normal pregnancies (Fig. 1, Supplementary Data S1). The subsequent analysis included genes with >0 FPKM (n = 22,896) and among these 20,983 genes (15,389 protein coding genes) exhibited expression > 0.1 FPKM (91.6%). Highest expression in both, normal and complicated pregnancies was observed for genes encoding small noncoding RNAs, including small nuclear RNAs contributing to pre-mRNA splicing and processing (e.g. RN7SK, RNU4-2, RNU4-1, RN7SL128P), small nucleolar RNAs involved in ribosomal RNA processing (e.g. SNORA73B, SNORD17) and small RNAs specific to Cajal body, a hallmark of proliferating cells (e.g. SCARNA10, SCARNA5) (Fig. 1a, Supplementary Data S1). Among the highest expressed placental transcripts is a highly conserved mammalian long noncoding RNA MALAT1, which regulates expression of genes implicated in cellular motility15, endothelial cell function and angiogenesis16. Its placental expression has not been previously studied.


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)

Top 20 transcripts((a) logarithmic scale) and protein coding genes ((b) linear scale) with the highest expression in placentas representing normal pregnancy (NORM) and cases of preeclampsia (PE), gestational diabetes (GD), small- and large-for-gestational-age newborns (SGA, LGA) (n = 8/group). Annotation of placental transcripts detected and quantified by the RNA-Seq pipeline was based on ENSEMBL v67 database. Gene expression levels are expressed in FPKM (fragments per kilobase of exons per million mapped fragments) as determined by cufflinks v 2.0.2. Data on the enrichment of gene expression in the placenta compared to other tissues was derived from Protein Atlas v12. Expression profile across tissues for noncoding RNAs was not available. Boxed gene names indicate transcripts ranked among the top-20 highest expressed genes only in specific pregnancy complications, comparative expression values of these transcripts in all studied groups are shown in Supplementary Fig. S3.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4542630&req=5

f1: Top 20 transcripts((a) logarithmic scale) and protein coding genes ((b) linear scale) with the highest expression in placentas representing normal pregnancy (NORM) and cases of preeclampsia (PE), gestational diabetes (GD), small- and large-for-gestational-age newborns (SGA, LGA) (n = 8/group). Annotation of placental transcripts detected and quantified by the RNA-Seq pipeline was based on ENSEMBL v67 database. Gene expression levels are expressed in FPKM (fragments per kilobase of exons per million mapped fragments) as determined by cufflinks v 2.0.2. Data on the enrichment of gene expression in the placenta compared to other tissues was derived from Protein Atlas v12. Expression profile across tissues for noncoding RNAs was not available. Boxed gene names indicate transcripts ranked among the top-20 highest expressed genes only in specific pregnancy complications, comparative expression values of these transcripts in all studied groups are shown in Supplementary Fig. S3.
Mentions: We ordered the genes by their median expression level, ranging from 0 to 40,923 FPKM (fragments per kilobase of exons per million mapped fragments) in placentas from normal pregnancies (Fig. 1, Supplementary Data S1). The subsequent analysis included genes with >0 FPKM (n = 22,896) and among these 20,983 genes (15,389 protein coding genes) exhibited expression > 0.1 FPKM (91.6%). Highest expression in both, normal and complicated pregnancies was observed for genes encoding small noncoding RNAs, including small nuclear RNAs contributing to pre-mRNA splicing and processing (e.g. RN7SK, RNU4-2, RNU4-1, RN7SL128P), small nucleolar RNAs involved in ribosomal RNA processing (e.g. SNORA73B, SNORD17) and small RNAs specific to Cajal body, a hallmark of proliferating cells (e.g. SCARNA10, SCARNA5) (Fig. 1a, Supplementary Data S1). Among the highest expressed placental transcripts is a highly conserved mammalian long noncoding RNA MALAT1, which regulates expression of genes implicated in cellular motility15, endothelial cell function and angiogenesis16. Its placental expression has not been previously studied.

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