Gene expression profile in endometrial organoids cultured in normal follicular phase vs PCOS-like hormone profile
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128328 | GEO | 2019/12/01
REPOSITORIES: GEO
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Project description:Context: Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer. Objective: We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial M-bM-^@M-^\disease phenotypeM-bM-^@M-^] affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny. Design and setting: A prospective study conducted at an academic medical center. Patients and Main Outcome Measures: Proliferative phase endometrium was obtained from 6 overweight/obese PCOS (NIH criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting (FACS)-isolated endometrial epithelial cells (eEP), endothelial cells (eEN), stromal fibroblasts (eSF) and mesenchymal stem cells (eMSC). Gene expression data were validated using microfluidic Q-RT-PCR and immunohistochemistry (IHC). Results: The comparison between eEPPCOS and eEPCtrl showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSFPCOS and eSFCtrl showed upregulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSCPCOS vs. eMSCCtrl the most upregulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). IHC scoring showed increased expression of CCL2 in eEPPCOS and eSFPCOS compared to eEPCtrl and eSFCtrl and IL-6 in eEPPCOS compared to eEPCtrl. Conclusions: Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and pro-oncogenic changes, independent of BMI, especially in eEPPCOS and eMSCPCOS, compared to controls. The study reveals an endometrial M-bM-^@M-^\disease phenotypeM-bM-^@M-^] in women with PCOS with potential negative effects on endometrial function and long-term health. Proliferative phase endometrium was obtained from 6 overweight/obese PCOS (NIH criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting (FACS)-isolated endometrial epithelial cells (eEP), endothelial cells (eEN), stromal fibroblasts (eSF) and mesenchymal stem cells (eMSC). Tissue samples were obtained through the National Institute of Health (NIH)/University of California, San Francisco (UCSF), Human Endometrial Tissue and DNA Bank in accordance with the guidelines of the Declaration of Helsinki. Informed consent was obtained from all participants in the UCSF Center for Reproductive Health, and the study was approved by the UCSF Committee on Human Research. The clinical summary of the study participants is shown in Table 1. Eleven proliferative phase endometrial biopsies (Pipelle, Cooper Surgical Shelton, Connecticut) and one curettage specimen were collected from over-weight (Body Mass Index [BMI, kg/m2] M-bM-^IM-% 27 < 29.9; n=1) and obese (BMI M-bM-^IM-% 30; n=5) women with PCOS (age 30.5M-BM-1 2.1 yrs, BMI 34.13M-BM-1 2.2, NIH criteria (17) and overweight (n=2) and obese (n=4) control women (age 36.50M-BM-11.70 yrs, BMI 35.73M-BM-13.96). All PCOS subjects had normal 17-hydroxyprogesterone, prolactin and thyroid hormone levels. Control samples were obtained from healthy volunteer and women undergoing benign gynecological surgery. All controls reported menstrual cycles with regular interval (25-35 days) and no clinical evidence of having PCOS. Neither PCOS nor control subjects were exposed to hormonal medications for at least 2 months prior to tissue sampling and were confirmed not pregnant.
2013-09-30 | E-GEOD-48301 | biostudies-arrayexpress
Project description:Background: Endometrial organoids are useful tools for studying endometrial biology but are derived from endoemtrial tissue obtained invasively from biopsies and mostly from women not taking hormonal medication. To increase the proportion of women from which endometrial organoids can be obtained, we sought to compare endometrial organoids derived from menstrual fluid and hormone-treated endometrium with standard endometrial organoids. Purpose: To determine if organoids derived from menstrual fluid and hormone-treated endometrium share features with standard endometrial organoids. Methods: RNA sequencing was performed on passage 3 day 7 menstrual fluid organoids (MFO), endometrial organoids from women taking hormonal medication (EMO-H) and standard endometrial organoids (EMO) Results: to determine if organoids derived from menstrual fluid and hormone-treated endometrium share features with staandard endometrial organoids. Conclusions: MFO and EMO-H did not cluster distinctly to EMO, indicating that they share features with EMO and may enable population-wide disease modelling. This is the first publicly available data set demonstrating the transcriptome of EMO-H.
2021-12-06 | GSE188915 | GEO
Project description:To reveal microRNAs expression differences in cumulus cells between polycystic ovary syndrome (PCOS) and non-PCOS women. miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS were determined by Affymetrix miRNA 2.0. Six pooled RNAs from CC samples (three PCOS and three non-PCOS pooled RNAs) were separately analyzed on 6 GeneChip miRNA 2.0 Array (miRBase V15)
2015-04-28 | E-GEOD-68285 | biostudies-arrayexpress
Project description:To reveal microRNAs expression differences in cumulus cells between polycystic ovary syndrome (PCOS) and non-PCOS women. miRNAs expression profile of the cumulus cell samples with PCOS and non-PCOS were determined by Affymetrix miRNA 2.0.
2015-04-28 | GSE68285 | GEO
Project description:Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder affecting women of reproductive age. The main features of PCOS are hyperandrogenism and irregular menstrual cycles together with metabolic dysfunctions including abdominal obesity, dyslipidemia and an increased risk of developing type 2 diabetes. Despite the high prevalence of >15%, the pathophysiology of the syndrome is unclear. Gene expression array data from skeletal muscle and adipose tissue have provided some information about dysregulated metabolic pathways in women with PCOS, but the transcriptomic data need to be verified by proteomics to advance our understanding of PCOS. Skeletal muscle and adipose tissue biopsies from 10 women with PCOS and 10 controls were subjected to global proteomic analysis. Protein expression differences between cases and controls were based on Student’s t-test and corrected for multiple testing. In total, we identified 5000 proteins in adipose tissue and 3480 proteins in skeletal muscle. After correction for multiple testing, 74 proteins with q < 0.05 corresponding to 72 unique proteins were found to be differentially expressed in adipose tissue from women with PCOS versus controls. And, 123 proteins with q < 0.05 corresponding to 120 unique proteins were found to be differentially expressed in skeletal muscle from women with PCOS versus control. We then applied pathway analysis to the total protein and phosphopeptide data using PRISM and Enrichr.
2024-01-09 | PXD025358 | Pride
Project description:The goal of the study was to assess transcriptome profile of non-decidualized (non-DE) and decidualized (DE) endometrial stromal cells (eSCs) obtained from women with polycystic ovary syndrome (PCOS, eSCPCOS) and non-PCOS controls (eSCCtrl) in response to short-term estradiol (E2) and/or progesterone (P4) exposure with or without dihydrotestosterone (DHT). The eSCs used for RNA-sequencing (RNA-seq) were isolated from proliferative stage endometrium from women with PCOS (diagnosed based on Rotterdam criteria) and non-PCOS controls (n=6 per group). The same eSCs were used for in vitro validation by immunofluorescence (IF; n=3/group). Tissue validation by immunohistochemistry (IHC) was done using whole biopsy formalin-fixed proliferative (PE) and secretory phase (SE) endometrial samples (IHC; n=6/cycle phase/group). Our data provided the observation that Decidualized eSCPCOS display a distinct transcriptome profile, especially in the presence of DHT.
2021-08-18 | GSE171507 | GEO
Project description:In this study, we sought to understand the effects of excess adipose on the benign endometrium. We used a physiologic in vitro coculture system consisting of multicellular organoids of the benign human endometrium and adipose spheroids in the presence of estradiol, progesterone, and testosterone to mimic the menstrual cycle. Gene expression analysis of endometrial organoids under high adiposity conditions revealed downregulation of genes normally expressed in secretory endometrium, suggestive of an altered progesterone response. Genes associated with ion homeostasis and detoxification of reactive oxygen species were also downregulated, including the metallothionein (MT) family of genes. We demonstrated that MT gene expression in endometrial organoids was regulated by progesterone specifically in the epithelial cells, and that progesterone receptor is recruited to the promoters of MT genes in endometrial epithelial cells. We illustrated the impact of MT dysregulation by silencing MT genes in endometrial epithelial cells, resulting in increased DNA damage. Our results reveal that exposing the endometrium to high adiposity can compromise the protective effects of progesterone, dysregulate MT genes in the endometrial epithelium, and leave the endometrium vulnerable to ROS-induced DNA damage.
2024-04-19 | GSE240926 | GEO
Project description:Polycystic Ovary Syndrome (PCOS) is a leading cause of infertility. About 5 million women in the US have PCOS, making it the most prevalent endocrine disorder among menstruating people. Despite that prevalence, the underlying causes remain unknown. Genome-wide association studies (GWAS) have identified non-coding genetic variation associated with PCOS risk and identifying the underlying molecular mechanisms is currently a major opportunity for improving diagnosis and treatment. We report the discovery of gene regulatory mechanisms that help explain genetic association with PCOS in the GATA4, FSHB and DENND1A loci. We based those findings using a combination of high throughput reporter assays, CRISPR-based epigenome editing, and genetic association analysis from PCOS case and control populations. In addition, we found that elevated endogenous DENND1A expression causes elevated testosterone levels, a hallmark PCOS phenotype. These results further highlight the potential for combining genetic variant analyses with experimental approaches to fine map genetic associations with disease risk.
2024-03-30 | GSE262471 | GEO
Project description:Gene expression profile in endometrial organoids cultured in normal follicular phase vs PCOS-like hormone profile
| PRJNA527131 | ENA
Project description:Context: Endometrium in polycystic ovary syndrome (PCOS) presents altered gene expression indicating progesterone resistance and predisposing to reduced endometrial receptivity and endometrial cancer. Objective: We hypothesized that an altered endocrine/metabolic environment in PCOS may result in an endometrial “disease phenotype” affecting the gene expression of different endometrial cell populations, including stem cells and their differentiated progeny. Design and setting: A prospective study conducted at an academic medical center. Patients and Main Outcome Measures: Proliferative phase endometrium was obtained from 6 overweight/obese PCOS (NIH criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting (FACS)-isolated endometrial epithelial cells (eEP), endothelial cells (eEN), stromal fibroblasts (eSF) and mesenchymal stem cells (eMSC). Gene expression data were validated using microfluidic Q-RT-PCR and immunohistochemistry (IHC). Results: The comparison between eEPPCOS and eEPCtrl showed dysregulation of inflammatory genes and genes with oncogenic potential (CCL2, IL-6, ORM1, TNAIFP6, SFRP4, SPARC). eSFPCOS and eSFCtrl showed upregulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSCPCOS vs. eMSCCtrl the most upregulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). IHC scoring showed increased expression of CCL2 in eEPPCOS and eSFPCOS compared to eEPCtrl and eSFCtrl and IL-6 in eEPPCOS compared to eEPCtrl. Conclusions: Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and pro-oncogenic changes, independent of BMI, especially in eEPPCOS and eMSCPCOS, compared to controls. The study reveals an endometrial “disease phenotype” in women with PCOS with potential negative effects on endometrial function and long-term health.
2013-09-30 | GSE48301 | GEO