Molecular classification of human endometrial cycle stages by transcriptional profiling

Abstract

Endometrium is a dynamic tissue that undergoes cyclic changes each month, under the overall control of estrogen and progesterone. The aims of this study were to investigate the changing global gene expression profile of human endometrium during the menstrual cycle using microarray technology and to determine the correlation between histopathological evaluation and molecular profile of the samples. Standard two-colour cDNA microarrays were performed on the 43 samples against a common reference, using a 10.5 K cDNA glass slide microarray. The results were validated using real-time PCR. Analysis of expression data was carried out using parametric analysis of variance with Benjamini-Hochberg correction. Hierarchical clustering reveals a strong relationship between histopathology and transcriptional profile of the samples. The study identified 1452 genes that showed significant changes in expression (P< or =0.05) across the menstrual cycle, with 425 genes having changes that are at least 2-fold. The data were also independently analysed by a CSIRO algorithm called GeneRaVE that identified a small subset of genes whose expression profiles could be used to classify nearly all the biopsies into their correct cycle stage. We also identified and validated three genes [(natural cytotoxicity triggering receptor (NCR)3, fucosyl transferase (FUT)4 and Fyn-binding protein (FYB)] that had not been shown to have significant cyclic changes in the human endometrium, previously. We have shown for the first time that endometrial cycle stage prediction is possible based on global gene expression profile.

Identification and hormonal regulation of a novel form of NKp30 in human endometrial epithelium

“…1A). These results confirm and extend previous observations [1] by significantly increasing the sample number and utilizing conventional histopathological rather than molecular classification of the menstrual cycle.…”

“…Initial results demonstrating the NKp30 mRNA expression profile of human endometrium during the menstrual cycle confirmed and extended our earlier work [1]. The mRNA was significantly up-regulated during the late-secretory phase of the menstrual cycle, when there is a significant infiltration of NK cells into the endometrium.…”

“…To better understand the molecular mechanisms underlying these changes, we investigated the changing global gene expression profile of human endometrium during the menstrual cycle [1] and demonstrated that one of the genes up-regulated during the late secretory stage of the menstrual cycle was NKp30, a natural killer (NK) cell receptor.…”

“…Data from our transcriptional profiling of human endometrium showed that NKp30 mRNA was significantly upregulated during the late-secretory stage of the menstrual cycle [1]. The aims of this study were to investigate cyclic changes of NKp30 mRNA in human endometrium during the menstrual cycle, localize the protein and examine the hormonal regulation of NKp30 transcription and translation.…”

Significance of glutathione peroxidases in endometrium function: facts, hypotheses, and research perspectives

“…Вышеописанные события происходят в стромальных клетках эндометрия, которые в ответ на стероидный стимул продуцируют паракринные факторы, приводящие к митозам клеток эпителия мат-ки [16]. Существует ряд работ по изучению транс-крипционного профиля эндометрия человека в ходе менструального цикла и при нарушени-ях рецептивности эндометрия; при этом среди генов ферментов группы GPX исследователи наблюдают существенные изменения в актив-ности гена GPX3 [16][17][18][19][20]. GPX3-транскрипт имеет очень низкий уровень в эндометриаль-ной ткани в пролиферативной фазе менстру-ального цикла, тогда как в секреторной фазе, когда доминирует уровень прогестерона, уро-вень GPX3-транскрипта повышается в десятки раз [16].…”