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Transcriptional profiling of mouse uterus at pre-implantation stage under VEGF repression.

Ji Y, Lu X, Zhong Q, Liu P, An Y, Zhang Y, Zhang S, Jia R, Tesfamariam IG, Kahsay AG, Zhang L, Zhu W, Zheng Y - PLoS ONE (2013)

Bottom Line: Vascular endothelial growth factor (VEGF), as one of the major members, has been found to be important in endothelial cell growth and blood vessel development, as well as in non-endothelial cells.Among VEGF-regulated genes, up-regulated were associated with RNA polymerase III activity while down-regulated were strongly related with muscle development.Expression levels of the antisense transcripts were found tightly correlated with their sense expression levels, an indication of possibly non-specific transcripts generated around the active promoters and enhancers.

View Article: PubMed Central - PubMed

Affiliation: Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, China.

ABSTRACT
Uterus development during pre-implantation stage affects implantation process and embryo growth. Aberrant uterus development is associated with many human reproductive diseases. Among the factors regulating uterus development, vascular remodeling promoters are critical for uterus function and fertility. Vascular endothelial growth factor (VEGF), as one of the major members, has been found to be important in endothelial cell growth and blood vessel development, as well as in non-endothelial cells. VEGF mediation in reproduction has been broadly studied, but VEGF-induced transcriptional machinery during implantation window has not been systematically studied. In this study, a genetically repressed VEGF mouse model was used to analyze uterus transcriptome at gestation 2.5 (G2.5) by Solexa/Illumina's digital gene expression (DGE) system. A number of 831 uterus-specific and 2398 VEGF-regulated genes were identified. Gene ontology (GO) analysis indicated that genes actively involved in uterus development were members of collagen biosynthesis, cell proliferation and cell apoptosis. Uterus-specific genes were enriched in activities of phosphatidyl inositol phosphate kinase, histone H3-K36 demethylation and protein acetylation. Among VEGF-regulated genes, up-regulated were associated with RNA polymerase III activity while down-regulated were strongly related with muscle development. Comparable numbers of antisense transcripts were identified. Expression levels of the antisense transcripts were found tightly correlated with their sense expression levels, an indication of possibly non-specific transcripts generated around the active promoters and enhancers. The antisense transcripts with exceptionally high or low expression levels and the antisense transcripts under VEGF regulation were also identified. These transcripts may be important candidates in regulation of uterus development. This study provides a global survey on genes and antisense transcripts regulated by VEGF in the pre-implantation stage. Results will contribute to further study the candidate genes and pathways in regulating implantation process and related diseases.

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Validation of differentially expressed genes by qPCR.Representative genes were selected to validate the DGE results, (A) up-regulated genes and (B) down-regulated genes by VEGF repression. The Y-axis indicates the fold change of gene expression. Error bars represent standard error.
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pone-0057287-g008: Validation of differentially expressed genes by qPCR.Representative genes were selected to validate the DGE results, (A) up-regulated genes and (B) down-regulated genes by VEGF repression. The Y-axis indicates the fold change of gene expression. Error bars represent standard error.

Mentions: To validate the differentially expressed genes identified by DGE profiling, representative genes were confirmed by qPCR. The up-regulated genes included purinergic receptor P2Y, G-protein coupled, 14 (P2ry14), gap junction protein, beta 2 (Gjb2), oxytocin receptor (Oxtr) and carbonic anhydrase 2 (Car2) (Figure 8A). The down-regulated genes were VEGF, sulfotransferase family 1D, member 1 (Sult1d1), cytotoxic T lymphocyte-associated protein 2 alpha (Ctla2a), histidine decarboxylase (Hdc) and Indian hedgehog (Ihh) (Figure 8B). Pearson’s correlation coefficients (r) were 0.972 and 0.931 for up- and down-regulated genes respectively.


Transcriptional profiling of mouse uterus at pre-implantation stage under VEGF repression.

Ji Y, Lu X, Zhong Q, Liu P, An Y, Zhang Y, Zhang S, Jia R, Tesfamariam IG, Kahsay AG, Zhang L, Zhu W, Zheng Y - PLoS ONE (2013)

Validation of differentially expressed genes by qPCR.Representative genes were selected to validate the DGE results, (A) up-regulated genes and (B) down-regulated genes by VEGF repression. The Y-axis indicates the fold change of gene expression. Error bars represent standard error.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3585347&req=5

pone-0057287-g008: Validation of differentially expressed genes by qPCR.Representative genes were selected to validate the DGE results, (A) up-regulated genes and (B) down-regulated genes by VEGF repression. The Y-axis indicates the fold change of gene expression. Error bars represent standard error.
Mentions: To validate the differentially expressed genes identified by DGE profiling, representative genes were confirmed by qPCR. The up-regulated genes included purinergic receptor P2Y, G-protein coupled, 14 (P2ry14), gap junction protein, beta 2 (Gjb2), oxytocin receptor (Oxtr) and carbonic anhydrase 2 (Car2) (Figure 8A). The down-regulated genes were VEGF, sulfotransferase family 1D, member 1 (Sult1d1), cytotoxic T lymphocyte-associated protein 2 alpha (Ctla2a), histidine decarboxylase (Hdc) and Indian hedgehog (Ihh) (Figure 8B). Pearson’s correlation coefficients (r) were 0.972 and 0.931 for up- and down-regulated genes respectively.

Bottom Line: Vascular endothelial growth factor (VEGF), as one of the major members, has been found to be important in endothelial cell growth and blood vessel development, as well as in non-endothelial cells.Among VEGF-regulated genes, up-regulated were associated with RNA polymerase III activity while down-regulated were strongly related with muscle development.Expression levels of the antisense transcripts were found tightly correlated with their sense expression levels, an indication of possibly non-specific transcripts generated around the active promoters and enhancers.

View Article: PubMed Central - PubMed

Affiliation: Transgenic Research Center, School of Life Sciences, Northeast Normal University, Changchun, China.

ABSTRACT
Uterus development during pre-implantation stage affects implantation process and embryo growth. Aberrant uterus development is associated with many human reproductive diseases. Among the factors regulating uterus development, vascular remodeling promoters are critical for uterus function and fertility. Vascular endothelial growth factor (VEGF), as one of the major members, has been found to be important in endothelial cell growth and blood vessel development, as well as in non-endothelial cells. VEGF mediation in reproduction has been broadly studied, but VEGF-induced transcriptional machinery during implantation window has not been systematically studied. In this study, a genetically repressed VEGF mouse model was used to analyze uterus transcriptome at gestation 2.5 (G2.5) by Solexa/Illumina's digital gene expression (DGE) system. A number of 831 uterus-specific and 2398 VEGF-regulated genes were identified. Gene ontology (GO) analysis indicated that genes actively involved in uterus development were members of collagen biosynthesis, cell proliferation and cell apoptosis. Uterus-specific genes were enriched in activities of phosphatidyl inositol phosphate kinase, histone H3-K36 demethylation and protein acetylation. Among VEGF-regulated genes, up-regulated were associated with RNA polymerase III activity while down-regulated were strongly related with muscle development. Comparable numbers of antisense transcripts were identified. Expression levels of the antisense transcripts were found tightly correlated with their sense expression levels, an indication of possibly non-specific transcripts generated around the active promoters and enhancers. The antisense transcripts with exceptionally high or low expression levels and the antisense transcripts under VEGF regulation were also identified. These transcripts may be important candidates in regulation of uterus development. This study provides a global survey on genes and antisense transcripts regulated by VEGF in the pre-implantation stage. Results will contribute to further study the candidate genes and pathways in regulating implantation process and related diseases.

Show MeSH
Related in: MedlinePlus