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| Status |
Public on Sep 30, 2013 |
| Title |
Mesenchymal Stem/Progenitors and Other Endometrial Cell Types from Women with Polycystic Ovary Syndrome (PCOS) Display Inflammatory and Oncogenic Potential |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
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.
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| Overall design |
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] ≥ 27 < 29.9; n=1) and obese (BMI ≥ 30; n=5) women with PCOS (age 30.5± 2.1 yrs, BMI 34.13± 2.2, NIH criteria (17) and overweight (n=2) and obese (n=4) control women (age 36.50±1.70 yrs, BMI 35.73±3.96). 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.
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| Contributor(s) |
Piltonen TT, Chen JC, Erikson DW, Spitzer TL, Barragan F, Rabban JT, Huddleston HG, Irwin JC, Giudice LC |
| Citation(s) |
23824412 |
| Submission date |
Jun 26, 2013 |
| Last update date |
Jul 26, 2018 |
| Contact name |
Linda Giudice |
| E-mail(s) |
giudice@obgyn.ucsf.edu
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| Phone |
415-476-2039
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| Organization name |
University of California, San Francisco
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| Department |
OBGYN and RS
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| Lab |
Giudice Lab
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| Street address |
513 Parnassus Ave. HSE 1619
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94122 |
| Country |
USA |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (29)
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| GSM1174408 |
Control Endometrium Mesenchymal Cell_ETB65 ++ |
| GSM1174409 |
Control Endometrium Endothelial Cell_ETB65 +- |
| GSM1174410 |
Control Endometrium Stromal Cell_ETB65 -+ |
| GSM1174411 |
Control Endometrium Stromal Cell_013.UC182-+ |
| GSM1174412 |
Control Endometrium Epithelial Cell_014.UC182_EpCAM |
| GSM1174413 |
Control Endometrium Mesenchymal Cell_015.UC182++new |
| GSM1174414 |
Control Endometrium Endothelial Cell_016.UC182+-new |
| GSM1174415 |
Control Endometrium Stromal Cell_029.UC208-+ |
| GSM1174416 |
Control Endometrium Epithelial Cell_030.UC208_EpCAM |
| GSM1174417 |
Control Endometrium Mesenchymal Cell_031.UC208++ |
| GSM1174418 |
Control Endometrium Endothelial Cell_032.UC208+- |
| GSM1174419 |
Control Endometrium Epithelial Cell_034.UC209_EpCAM |
| GSM1174420 |
Control Endometrium Mesenchymal Cell_035.UC209++) |
| GSM1174421 |
Control Endometrium Endothelial Cell_036.UC209+- |
| GSM1174422 |
Control Endometrium Stromal Cell_033.UC-209-+ |
| GSM1174423 |
PCOS Endometrium Stromal Cell_101.PC01-+ |
| GSM1174424 |
PCOS Endometrium Mesenchymal Cell_102.PC01++ |
| GSM1174425 |
PCOS Endometrium Endothelial Cell_103.PC01+- |
| GSM1174426 |
PCOS Endometrium Stromal Cell_104.PC07-+ |
| GSM1174427 |
PCOS Endometrium Epithelial Cell_105.PC07_EpCAM |
| GSM1174428 |
PCOS Endometrium Mesenchymal Cell_106.PC07++ |
| GSM1174429 |
PCOS Endometrium Endothelial Cell_107.PC07+- |
| GSM1174430 |
PCOS Endometrium Epithelial Cell_109.PC08_EpCAM |
| GSM1174431 |
PCOS Endometrium Stromal Cell_118.PC11-+ |
| GSM1174432 |
PCOS Endometrium Epithelial Cell_119.PC11_EpCAM |
| GSM1174433 |
PCOS Endometrium Mesenchymal Cell_120.PC11++ |
| GSM1174434 |
PCOS Endometrium Stromal Cell_134.UC271-+ |
| GSM1174435 |
PCOS Endometrium Epithelial Cell_138.UC271 EpCAM |
| GSM1174436 |
PCOS Endometrium Endothelial Cell_140.UC271+- |
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| Relations |
| BioProject |
PRJNA209595 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE48301_RAW.tar |
113.0 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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