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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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KEGG analysis of VEGF-regulated genes.Genes with expression level higher than 200 copies (Dox+ plus Dox− ≥200) were used. Pathway analysis was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Y-axis represents the pathway category and the X-axis represents the log10 (p-value) of the significant pathways.
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pone-0057287-g006: KEGG analysis of VEGF-regulated genes.Genes with expression level higher than 200 copies (Dox+ plus Dox− ≥200) were used. Pathway analysis was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Y-axis represents the pathway category and the X-axis represents the log10 (p-value) of the significant pathways.

Mentions: KEGG analysis showed that up-regulated genes by VEGF repression were participating in proteasome, p53 signaling and progesterone-mediated oocyte maturation pathways (Figure 6A), indicating active protein degradation and apoptosis in developing uterus. Down-regulated genes were associated with valine, leucine, lysine degradation, propanoate, fatty acid, pyruvate metabolism and TCA cycle. Degradation and metabolic pathways were obviously down-regulated by VEGF repression (Figure 6B).


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)

KEGG analysis of VEGF-regulated genes.Genes with expression level higher than 200 copies (Dox+ plus Dox− ≥200) were used. Pathway analysis was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Y-axis represents the pathway category and the X-axis represents the log10 (p-value) of the significant pathways.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057287-g006: KEGG analysis of VEGF-regulated genes.Genes with expression level higher than 200 copies (Dox+ plus Dox− ≥200) were used. Pathway analysis was based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. The Y-axis represents the pathway category and the X-axis represents the log10 (p-value) of the significant pathways.
Mentions: KEGG analysis showed that up-regulated genes by VEGF repression were participating in proteasome, p53 signaling and progesterone-mediated oocyte maturation pathways (Figure 6A), indicating active protein degradation and apoptosis in developing uterus. Down-regulated genes were associated with valine, leucine, lysine degradation, propanoate, fatty acid, pyruvate metabolism and TCA cycle. Degradation and metabolic pathways were obviously down-regulated by VEGF repression (Figure 6B).

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