Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide expression analysis of autologous eutopic and ectopic endometrium from fertile Indian women with endometriosis

ABSTRACT: Whole genome expression analyses of autologous, paired eutopic and ectopic endometrial samples obtained during proliferative and secretory phases of menstrual cycles from eighteen (n=18) fertile women suffering from confirmed stage 3 (moderate) and stage 4 (severe) ovarian endometriosis were performed using whole human genome oligo microarray Agilent paltform (Cat. No. G4112F). In the present study, genome-wide expression analysis of autologous, paired eutopic and ectopic endometrial samples obtained during proliferative (n=13) and secretory (n=5) phases of menstrual cycle from fertile women (n=18) suffering from moderate (stage 3; n=8) or severe (stage 4; n=10) endometrioma was performed by using Agilent single color oligo microarray platform (G4112, 4X44K). Thus eighteen (18) eutopic (shown as EU) and eighteen (18) ectopic (shown as EC) samples from eighteen (18) subjects with confirmed menstrual phase (proliferative and secretory) and severity stages (stage 3 and stage 4) were studied.

ORGANISM(S): Homo sapiens

SUBMITTER: Meraj Khan

PROVIDER: E-GEOD-37837 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis.

Khan Meraj A MA Sengupta Jayasree J Mittal Suneeta S Ghosh Debabrata D

Reproductive biology and endocrinology : RB&E 20120924

<h4>Background</h4>In 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 eutopi ...[more]

PMID: 23006437

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Project description:Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected at 9-11 days postovulation) in five time points: 1, 3, 6-7, 10-12, and 15-16 months after disease induction and compared with tissue from disease-free baboons. We used microarrays to identify differentially expressed genes between time points. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype. However, as the disease progressed, a progesterone-resistant phenotype became evident. Endometriosis was experimentally induced in Papio anubis female baboons (n = 4) by intraperitoneal inoculation with menstrual endometrium on two consecutive menstrual cycles. Baboons with spontaneous endometriosis (n = 2) were also included in this study with an unknown duration of disease. Control endometrium was similarly harvested from animals (n = 4) with no previous surgeries and with no visible disease. The progression of disease was monitored in each animal by consecutive laparoscopies and video recording at 1 (n = 2), 3 (n = 4), 6-7 (n = 4), 10-12, (n = 4), and 15-16 (n = 3) months after inoculation during a window of 9-11 days postovulation. Eutopic endometrial tissues were harvested and were snap frozen in liquid nitrogen for RNA extraction. Additionally, menstrual endometrium was harvested on Days 1-2 of menses using a Unimar Pipelle (Cooper Surgical Inc., Shelton, CT) immediately prior to laparoscopy. Blood samples were collected daily from days 7 through 16 postmenstruation of menstrual cycles.

Project description:Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. Abstract: Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis. Design: Laboratory-based study with full IRB approval and consents. Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically-confirmed diffuse adenomyosis (n=3). Controls (n=5) were normo-ovulatory subjects without adenomyosis. All subjects were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by QRT-PCR. Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 up-regulated and 884 down-regulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptopsis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling, as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mTOR signaling. Conclusions: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface. Key Words: adenomyosis, endometrium, microarray, microRNA, endometriosis, apoptosis, signaling. A total of 8 samples were used and analyzed by disease state. Endometrial samples from hysterectomy specimens in proliferative phase of menstrual cycle from symptomatic women with pathologically-confirmed diffuse adenomyosis were compared with endometrial samples from normo-ovulatory healthy subjects with no endometrial or uterine pathology.

Dataset Information

Genome-wide expression analysis of autologous eutopic and ectopic endometrium from fertile Indian women with endometriosis

Publications

Genome-wide expressions in autologous eutopic and ectopic endometrium of fertile women with endometriosis.

Similar Datasets

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