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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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GO analysis of down-regulated genes by VEGF repression.
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pone-0057287-g005: GO analysis of down-regulated genes by VEGF repression.

Mentions: In order to study the mechanism of VEGF regulating implantation process and identify the genes that VEGF may regulate, the transcription profile of pre-implantation uterus was compared between Dox+ and Dox− samples. The cutoff of the combined copy number of each gene was ≥200 and minimum fold change was 1.5. A total of 2398 differentially expressed genes, 1231 up- and 1167 down-regulated, were identified. There were 302 up- and 368 down-regulated genes with fold change ≥2, 42 up- and 49 down-regulated genes with fold change ≥5 (Figure S7). Highly expressed and VEGF-regulated genes were listed in Table 2, Table S2 and Table S3. High percentages of up-regulated genes were found in the categories of ribonucleoside diphosphate biosynthetic process, cytokinesis, TGFβ pathway, regulation of tissue remodeling and RNA polymerase III function (Figure 4). Down-regulated genes were strongly associated with regulation of skeletal muscle tissue development, muscle fiber development, striated muscle cell development and fibronectin binding as shown in Figure 5. These results demonstrated VEGF might regulate muscle tissue remodeling. Previous studies have reported that TGFβ signaling pathway plays important roles in controlling apoptosis and cell survival during pregnancy [28].


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)

GO analysis of down-regulated genes by VEGF repression.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0057287-g005: GO analysis of down-regulated genes by VEGF repression.
Mentions: In order to study the mechanism of VEGF regulating implantation process and identify the genes that VEGF may regulate, the transcription profile of pre-implantation uterus was compared between Dox+ and Dox− samples. The cutoff of the combined copy number of each gene was ≥200 and minimum fold change was 1.5. A total of 2398 differentially expressed genes, 1231 up- and 1167 down-regulated, were identified. There were 302 up- and 368 down-regulated genes with fold change ≥2, 42 up- and 49 down-regulated genes with fold change ≥5 (Figure S7). Highly expressed and VEGF-regulated genes were listed in Table 2, Table S2 and Table S3. High percentages of up-regulated genes were found in the categories of ribonucleoside diphosphate biosynthetic process, cytokinesis, TGFβ pathway, regulation of tissue remodeling and RNA polymerase III function (Figure 4). Down-regulated genes were strongly associated with regulation of skeletal muscle tissue development, muscle fiber development, striated muscle cell development and fibronectin binding as shown in Figure 5. These results demonstrated VEGF might regulate muscle tissue remodeling. Previous studies have reported that TGFβ signaling pathway plays important roles in controlling apoptosis and cell survival during pregnancy [28].

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