Mesenchymal Stem/Progenitors and Other Endometrial Cell Types From Women With Polycystic Ovary Syndrome (PCOS) Display Inflammatory and Oncogenic Potential

• Published in: The journal of clinical endocrinology and metabolism 2013-09, Vol.98 (9), p.3765-3775
• Main Authors: Piltonen, T. T, Chen, J, Erikson, D. W, Spitzer, T. L. B, Barragan, F, Rabban, J. T, Huddleston, H, Irwin, J. C, Giudice, L. C
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Body Mass Index; Cell Proliferation; Endocrine Research; Endocrinopathies; Endometrium - metabolism; Endometrium - pathology; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Humans; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Interleukin-6 - genetics; Interleukin-6 - metabolism; Interleukin-8 - genetics; Interleukin-8 - metabolism; Medical sciences; Mesenchymal Stromal Cells - metabolism; Mesenchymal Stromal Cells - pathology; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Overweight - genetics; Overweight - metabolism; Overweight - pathology; Polycystic Ovary Syndrome - genetics; Polycystic Ovary Syndrome - metabolism; Polycystic Ovary Syndrome - pathology; Up-Regulation; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2013-1923

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: This was a prospective study conducted at an academic medical center. Patients and Main Outcome Measures: Proliferative-phase endometrium was obtained from 6 overweight/obese PCOS (National Institutes of Health criteria) and 6 overweight/obese controls. Microarray analysis was performed on fluorescence-activated cell sorting-isolated endometrial epithelial cells (eEPs), endothelial cells, stromal fibroblasts (eSFs), and mesenchymal stem cells (eMSCs). Gene expression data were validated using microfluidic quantitative RT-PCR and immunohistochemistry. 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 up-regulation of inflammatory genes (C4A/B, CCL2, ICAM1, TNFAIP3). Similarly, in eMSCPCOS vs eMSCCtrl, the most up-regulated genes were related to inflammation and cancer (IL-8, ICAM1, SPRR3, LCN2). Immunohistochemistry scoring showed increased expression of CCL2 in eEPPCOS and eSFPCOS compared with eEPCtrl and eSFCtrl and IL-6 in eEPPCOS compared with eEPCtrl. Conclusions: Isolated endometrial cell populations in women with PCOS showed altered gene expression revealing inflammation and prooncogenic changes, independent of body mass index, especially in eEPPCOS and eMSCPCOS, compared with controls. The study reveals an endometrial disease phenotype in women with PCOS with potential negative effects on endometrial function and long-term health.