Determination of the transcript profile of human endometrium

Abstract

The response of the human endometrium to the ovarian hormones, estrogen and progesterone, has been the focus of decades of research. In order to understand this critical aspect of endometrial physiology, we undertook a genome-wide analysis of transcript abundance and changes in transcript level between normal endometrium in the proliferative and secretory phases of the menstrual cycle. A high-density, oligonucleotide gene array, comprising 60 000 gene targets, was used to define the gene expression profile of proliferative and secretory phase endometrium. Results from the arrays were verified using real-time PCR. The expression levels of 149 transcripts differed significantly between the two phases of the cycle determined by stringent range limits (99.99%), calculated using local variance values. These transcripts include previously documented steroidally responsive genes (such as placental protein 14 and stromelysin-3) and novel transcripts not previously linked to either endometrial physiology or steroid regulation (such as intestinal trefoil factor and a number of expressed sequence tags). Examination of the 5' promoter regions of these genes identified many putative estrogen and progesterone receptor DNA binding domains, suggesting a direct response of these genes to the ovarian hormones.

Trefoil factor 3: a novel serum marker identified by gene expression profiling in high-grade endometrial carcinomas

“…Accordingly, Madsen et al (2007) found few endometrial cells positively stained for TFF3 by immunohistochemistry. In contrast, Borthwick et al (2003) documented different TFF3 transcript levels during the phases of the menstrual cycle, with a major TFF3 expression in proliferative compared with secretory endometrium, suggesting its role in regeneration of the human endometrium following menstruation.…”

Uterine receptivity to human embryonic implantation: Histology, biomarkers, and transcriptomics

“…However, caveats include reactive inflammatory changes and subsequent gene alterations as a result of the first biopsy [56], and different microenvironments and/or complement of cell types may be represented in the two biopsies from the same subject. Figure 1 represents the distribution of significantly changed genes among different groups of genes in the studies by Kao et al [52], Carson et al [53], Borthwick et al [55], Riesewijk et al [54] and Mirkin et al [56]. Genes with unknown biological function represented one of the biggest groups of regulated genes.…”

“…Five studies were published, within a short time frame, reporting the transcriptome human endometrium during the window of implantation [52][53][54][55][56] (Table 1). Remarkably, all studies used the same microarray platform to perform their analysis.…”

“…This makes a comparison between the studies possible; however, there are differences in the type of data analysis, as well as number of patient samples used, ages of subjects, cycle phases compared, and pooling or not pooling samples (Table I). Two studies [53,55] pooled RNA from different patients to run on microarrays. Four out of five studies [52,53,55,56] used pre-defined fold change cut off of 2.0 as evidence of change in gene regulation, while Riesewijk et al [54] used a more stringent approach and a 3.0 fold change as a cutoff.…”

“…Two studies [53,55] pooled RNA from different patients to run on microarrays. Four out of five studies [52,53,55,56] used pre-defined fold change cut off of 2.0 as evidence of change in gene regulation, while Riesewijk et al [54] used a more stringent approach and a 3.0 fold change as a cutoff. The latter study is the only one that analyzed samples from the same woman in the early and the mid-secretory phase of the menstrual cycle.…”