The Different Gene Expression Profile in the Eutopic and Ectopic Endometrium Sheds New Light on the Endometrial Seed in Endometriosis
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ABSTRACT:
SUBMITTER: Riaz M
PROVIDER: S-EPMC11201009 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:PROBLEM: As recent studies have suggested abnormalities in the regulation of specific genes in the development of endometriosis, we investigated differentially expressed genes in endometriosis compared to endometrium. METHOD OF STUDY: Gene expression profiles using the Atlas microarray were performed in endometriotic tissue and endometrium. Nine of the 13 genes of endometriotic tissue showed an up-regulation in relation to endometrium and four of the 13 genes a down-regulation. RESULTS: Of the 1176 genes on the Atlas Human 1,2 array, only 13 differentially expressed identical genes were detected after repeating the gene analysis three times. CONCLUSION: According to our c-DNA analysis some differentially expressed genes may be involved in the pathogenesis of endometriosis. An imbalance in the genes responsible for the reproductive process may lead to a decrease in embryo implantation in patients with endometriosis.
| S-EPMC3454973 | biostudies-literature
Project description:BackgroundIn order to obtain a lead of the pathophysiology of endometriosis, genome-wide expressional analyses of eutopic and ectopic endometrium have earlier been reported, however, the effects of stages of severity and phases of menstrual cycle on expressional profiles have not been examined. The effect of genetic heterogeneity and fertility history on transcriptional activity was also not considered. In the present study, a genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained from fertile women (n=18) suffering from moderate (stage 3; n=8) or severe (stage 4; n=10) ovarian endometriosis during proliferative (n=13) and secretory (n=5) phases of menstrual cycle was performed.MethodsIndividual pure RNA samples were subjected to Agilent's Whole Human Genome 44K microarray experiments. Microarray data were validated (P<0.01) by estimating transcript copy numbers by performing real time RT-PCR of seven (7) arbitrarily selected genes in all samples. The data obtained were subjected to differential expression (DE) and differential co-expression (DC) analyses followed by networks and enrichment analysis, and gene set enrichment analysis (GSEA). The reproducibility of prediction based on GSEA implementation of DC results was assessed by examining the relative expressions of twenty eight (28) selected genes in RNA samples obtained from fresh pool of eutopic and ectopic samples from confirmed ovarian endometriosis patients with stages 3 and 4 (n=4/each) during proliferative and secretory (n=4/each) phases.ResultsHigher clustering effect of pairing (cluster distance, cd=0.1) in samples from same individuals on expressional arrays among eutopic and ectopic samples was observed as compared to that of clinical stages of severity (cd=0.5) and phases of menstrual cycle (cd=0.6). Post hoc analysis revealed anomaly in the expressional profiles of several genes associated with immunological, neuracrine and endocrine functions and gynecological cancers however with no overt oncogenic potential in endometriotic tissue. Dys-regulation of three (CLOCK, ESR1, and MYC) major transcription factors appeared to be significant causative factors in the pathogenesis of ovarian endometriosis. A novel cohort of twenty-eight (28) genes representing potential marker for ovarian endometriosis in fertile women was discovered.ConclusionsDysfunctional expression of immuno-neuro-endocrine behaviour in endometrium appeared critical to endometriosis. Although no overt oncogenic potential was evident, several genes associated with gynecological cancers were observed to be high in the expressional profiles in endometriotic tissue.
| S-EPMC3533745 | biostudies-literature
Project description:Endometriosis is defined as the presence of endometrial tissue (eutopic tissue) outside the uterus (ectopic tissue). We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium. Comparison of paired eutopic/ectopic endometrium microRNAs from three patients.
2010-12-30 | E-GEOD-26346 | biostudies-arrayexpress
Project description:Endometriosis is a common gynecological disorder characterized by pain and infertility, where the lesions disseminate everywhere in the body with a preference for the pelvis. In that, it could be regarded as a âbenign metastatic diseaseâ, since its issue is not fatal. However, the molecular bases of this intriguing clinical condition are not well known. The objective of this study is to characterize the transcriptome differences between eutopic vs ectopic endometrium with a special interest in pathways involved in cancerogenesis. We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGenâ¢), with cDNA prepared from 6-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas). In order to confirm the expression microarrays data, qRT-PCR validation was performed on 12 individuals for 20 genes. Over 8,000 transcripts were significantly modified (more than twice) in the lesions corresponding to 5,600 down- or up-regulated genes. These were clustered through DAVID Bioinformatics Resources into 55 functional groups. The data are presented in a detailed and visual way on 24 KEGG pathways implemented with induction ratios for each differentially expressed gene. An outstanding control of the cell cycle and a very specific modulation of the HOX genes were observed and provide some new evidence on why endometriosis only very rarely degenerates into cancer. The study constitutes a noteworthy update of gene profiling in endometriosis, by delivering the most complete and reliable list of dysregulated genes to date. Keywords: Gene expression microarrays We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGenâ¢), with cDNA prepared from 6-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas)
2010-06-19 | E-GEOD-12768 | biostudies-arrayexpress
Project description:Endometriosis is a common gynecological disorder characterized by pain and infertility, where the lesions disseminate everywhere in the body with a preference for the pelvis. In that, it could be regarded as a “benign metastatic disease”, since its issue is not fatal. However, the molecular bases of this intriguing clinical condition are not well known. The objective of this study is to characterize the transcriptome differences between eutopic vs ectopic endometrium with a special interest in pathways involved in cancerogenesis. We performed two hybridizations in technical replicate on highly specific long oligonucleotides microarrays (NimbleGen™), with cDNA prepared from 6-patients pools, where the same patient provided both eutopic and ectopic endometrium (endometriomas). In order to confirm the expression microarrays data, qRT-PCR validation was performed on 12 individuals for 20 genes. Over 8,000 transcripts were significantly modified (more than twice) in the lesions corresponding to 5,600 down- or up-regulated genes. These were clustered through DAVID Bioinformatics Resources into 55 functional groups. The data are presented in a detailed and visual way on 24 KEGG pathways implemented with induction ratios for each differentially expressed gene. An outstanding control of the cell cycle and a very specific modulation of the HOX genes were observed and provide some new evidence on why endometriosis only very rarely degenerates into cancer. The study constitutes a noteworthy update of gene profiling in endometriosis, by delivering the most complete and reliable list of dysregulated genes to date. Keywords: Gene expression microarrays
2008-09-13 | GSE12768 | GEO
Project description:Endometriosis is defined as the presence of endometrial tissue (eutopic tissue) outside the uterus (ectopic tissue). We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium.
2010-12-30 | GSE26346 | GEO
Project description:Comparison of macrophages M1 (M1) and M2 (M2) from eutopic endometrium from women with and without endometriosis
2020-01-22 | GSE130435 | GEO
Project description:About 40% of women with infertility and 70% of women with pelvic pain suffer from endometriosis. The pregnancy rate in women undergoing IVF with low endometrial integrin αvβ3 (LEI) expression is significantly lower compared to the women with high endometrial integrin αvβ3 (HEI). Mid-secretory eutopic endometrial biopsies were obtained from healthy controls (C; n=3), and women with HEI (n=4) and LEI (n=4) and endometriosis. Changes in gene expression were assessed using human gene arrays and DNA methylation data were derived using 385 K Two-Array Promoter Arrays. Transcriptional analysis revealed that LEI and C groups clustered separately with 396 differentially expressed genes (DEGs) (P<0.01: 275 up and 121 down) demonstrating that transcriptional and epigenetic changes are distinct in the LEI eutopic endometrium compared to the C and HEI group. In contrast, HEI vs C and HEI vs LEI comparisons only identified 83 and 45 DEGs, respectively. The methylation promoter array identified 1304 differentially methylated regions in the LEI vs C comparison. The overlap of gene and methylation array data identified 14 epigenetically dysregulated genes and quantitative RT-PCR analysis validated the transcriptomic findings. The analysis also revealed that aryl hydrocarbon receptor (AHR) was hypomethylated and significantly overexpressed in LEI samples compared to C. Further analysis validated that AHR transcript and protein expression are significantly (P<0.05) increased in LEI women compared to C. The increase in AHR, together with the altered methylation status of the 14 additional genes, may provide a diagnostic tool to identify the subset of women who have endometriosis-associated infertility.
| S-EPMC8178932 | biostudies-literature
Project description:Endometriosis is a common gynecological disease that affects approximately 5-10% of reproductive-aged women. However, the etiology and pathophysiology of endometriosis are currently unclear. The objective of this study was to identify a potential pathogenic gene of endometriosis using RNA sequencing (RNA-seq) analysis. Human endometrial stromal cells were isolated from four patients receiving surgical treatment for endometriosis during laparoscopic surgery, and RNA-seq was used to examine differentially expressed genes (DEGs) in eutopic and ectopic endometrial stromal cells. The functional significance of the differentially expressed genes was analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A total of 1309 upregulated and 663 downregulated genes were identified through the analysis of the transcriptomes of eutopic and ectopic endometrial stromal cells. Furthermore, KEGG analysis indicated that these DEGs were mainly enriched in the PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, and MAPK signaling pathway. Our study identified differential gene expression in eutopic as compared to ectopic endometrial tissue stromal cells. We strongly believe that our findings can bring new insights into the underlying mechanisms of endometriosis. However, future research is necessary to clarify the roles of the identified genes.
| S-EPMC9598494 | biostudies-literature
Project description: Not available
| S-EPMC6595869 | biostudies-literature