Transcriptional Profiling of Mouse Uterus at Pre-Implantation Stage under VEGF Repression

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.

Brazilin induces T24 cell death through c‐Fos and GADD45β independently regulated genes and pathways

“…Gain and loss of gene function are the basic techniques used for gene function studies and drug‐target screening. RNA‐Seq, which is based on the second‐generation sequencing technology can provided accurate and high throughput measurement of gene expression and are increasingly used in gene regulation studies. In this study, we analyzed the inhibitory effect of c‐Fos and GADD45β on T24 cells, through transfection and comparative transcriptomic analysis.…”

Keratin 86 is up-regulated in the uterus during implantation, induced by oestradiol

“…There are few reports on the expression and function of KRT86 in the uterus; however, some information can be obtained from homologues. For example, KRT85, another member of the keratin family, is also expressed in the uterus [16]. Like KRT86, it also forms type II hair keratin and nails, and is a basic protein [17].…”

“…Like KRT86, it also forms type II hair keratin and nails, and is a basic protein [17]. In a vascular endothelial growth factor (VEGF) regulating implantation model, VEGF repression caused implantation failure, and Krt85 is dramatically up-regulated (1000 fold), indicating a role of keratin during implantation [16]. In alopecia areata (AA) lesional skin, Krt85 and Krt86 were significantly repressed [18].…”

Vascular endothelial growth factor induces anti-Müllerian hormone receptor 2 overexpression in ovarian granulosa cells of in vitro fertilization/intracytoplasmic sperm injection patients

“…It has been proposed that VEGF, by regulating vascular permeability, induces blood vessel leaking in ovaries exhibiting ovarian hyperstimulation syndrome (OHSS) (13). Notably, in a transgenic mouse model with engineered inducible repression of VEGF, mice were observed to become infertile upon VEGF repression (14 2,398 VEGF-regulated differentially expressed genes were identified in the mouse uterus, which indicated that VEGF exerts a regulatory role in gene expression in the uterus. The majority of studies regarding AMH focus on the early stage of follicle development.…”