Neuroendocrine characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.
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ABSTRACT:
SUBMITTER: Min Z
PROVIDER: S-EPMC6588674 | biostudies-literature | 2019 Jul
REPOSITORIES: biostudies-literature
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Neuroendocrine characteristics of induced pluripotent stem cells from polycystic ovary syndrome women.
Min Zheying Z Zhao Yue Y Hang Jing J Ren Yun Y Tan Tao T Fan Yong Y Yu Yang Y
Protein & cell 20190701 7
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Project description:In the original publication the Fig. 2 and the Supplementary Material 1 was incorrect. The correct version of Fig. 2 and the Supplementary Material are provided in this correction article. NESTIN should be corrected to PAX6 in Fig. 2C legend and at page 528 and Supplementary Material 1. NANOG should be corrected to PAX6 in Fig. 2C picture. Fig. 2. Differentiation and identification of NSCs from PCOS-derived iPSCs. (A) Schematic procedure of NSCs differentiation from iPSCs. NSC: Neural stem cell; EB: embryoid body. (B) The phenotype of specific differentiated NSCs. Scale bars = 100 µm. (C) Immunofluorescence images of the NSC markers SOX2 and PAX6. Scale bars = 50 µm. ZOOM, scale bars = 25 μm. (D) The mitochondrial respiration function of PCOS- and non-PCOS-derived iPSCs and NSCs. (E) Quantitative analysis of basal oxygen consumption, ATP production, maximal respiration, and proton leak. (F) Proposed neuroendocrine state in normal and PCOS patients. In normal patients, the GnRH pulsatile frequency is critical for steroidogenesis and follicular development. Low frequency pulses prefer FSH, and high frequency pulses favour LH. In PCOS, the increased GnRH release led to a high level of LH pulsatility, impairing the preferential release of FSH and follicular maturation, thus leading to polycystic ovaries. Red: increased; Blue: decreased. Solid arrow: up regulated; Dotted arrow: down regulated.
| S-EPMC7026241 | biostudies-literature
Project description:BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects female fertility. However, with the lack of a corresponding research model, the pathology mechanism of PCOS is poorly understood. Induced pluripotent stem cell (iPSC) technology has been recognized as means to generate patient-specific stem cells for disease modeling.MethodsThe mRNA abundance of iPSCs was analyzed by RNA microarray and real-time polymerase chain reaction (RT-PCR). Karyotyping of iPSCs was performed with cytogenetic analysis. The mitochondrial respiration ability and glycolytic function were measured by the Seahorse Bioscience XF extracellular flux analyzer. The expression of iPSC-associated markers was identified by immunofluorescence and RT-PCR. The teratoma formation of iPSCs was studied using immunochemistry.ResultsA PCOS patient-derived iPSC model was established from somatic cells of PCOS patients. Through comprehensive transcriptional profiling analysis of the RNA microarray, PCOS patient-derived iPSCs showed metabolic abnormalities and mitochondrial dysfunction compared with non-PCOS patient-derived iPSCs in vitro. Specifically, a total of 2904 genes were differentially expressed between the two iPSC populations, of which 1416 genes were upregulated and 1488 genes were downregulated (fold change > 2, p < 0.01). Gene Ontology (GO) term enrichment results showed that upregulated genes were enriched in metabolic processes and mitochondrial activities which participated in the tricarboxylic acid (TCA) cycle, the respiratory electron transport chain (ETC), and glycogenolysis. On the other hand, the downregulated genes were related to cell communication, glucose transport, and uptake. The differentially expressed genes were verified by RT-PCR in PCOS patient-derived iPSCs and granulosa cells from PCOS patients. The PCOS patient-derived iPSCs demonstrated decreased mitochondrial respiration ability and glycolytic function (p < 0.05) but increased mitochondrial copy numbers and biogenesis (p < 0.05). Subsequently, some genes related to glucose metabolism were rescued by treating with metformin in PCOS patient-derived iPSCs. Meanwhile, the ATP production ability of mitochondria and the glycolysis ability of PCOS patient-derived iPSCs also partially returned to normal levels. However, metformin had little effect on mitochondrial maximal respiration ability and maximal glycolytic capacity.ConclusionsWe measured differences in iPSCs from women with and without PCOS in gene transcription and mitochondrial respiratory function. PCOS patient-derived iPSCs showed abnormal expression of metabolic genes and mitochondrial dysfunction in vitro. The study provides a novel cell model in vitro for studying the clinical causes and molecular mechanisms of PCOS.
| S-EPMC6085636 | biostudies-literature
Project description:ObjectiveTo establish a new biological cell model and approach to mimic abnormal lipid metabolism of polycystic ovary syndrome (PCOS) in vitro.Materials and methodsEpithelial cells from PCOS patients were reprogrammed to pluripotency by retroviral transduction using defined factors. Morphology, growth characteristics, karyotype, gene expression and differentiation in vitro and in vivo were detected by identification protocol of human embryonic stem cells (ESCs). PCOS-induced pluripotent stem cells (iPSCs) were then induced to differentiate into adipocytes. Ability of the adipocytes for glucose consumption was compared with those from non-PCOS-iPSCs.ResultsiPSCs were successfully generated from PCOS patients' adult cells. Formed iPSC clones had the same characteristics of human ESCs. PCOS-iPSCs were induced to differentiation into normal karyotype adipocytes. Compared to non-PCOS-iPSCs, PCOS-iPSCs had more glucose consumption ability during adipocyte differentiation and development in vitro.ConclusionsThis protocol provides a new biological cell model and approach for studying pathogenesis of PCOS and discovering potential drugs to treat it.
| S-EPMC6496004 | biostudies-literature
Project description:Polycystic ovary syndrome (PCOS) is the most prevalent endocrine condition among women with pleiotropic sequelae possessing reproductive, metabolic, and psychological characteristics. Although the exact origin of PCOS is elusive, it is known to be a complex multigenic disorder with a genetic, epigenetic, and environmental background. However, the pathogenesis of PCOS, and the role of genetic variants in increasing the risk of the condition, are still unknown due to the lack of an appropriate study model. Since the debut of induced pluripotent stem cell (iPSC) technology, the ability of reprogrammed somatic cells to self-renew and their potential for multidirectional differentiation have made them excellent tools to study different disease mechanisms. Recently, researchers have succeeded in establishing human in vitro PCOS disease models utilizing iPSC lines from heterogeneous PCOS patient groups (iPSCPCOS). The current review sets out to summarize, for the first time, our current knowledge of the implications and challenges of iPSC technology in comprehending PCOS pathogenesis and tissue-specific disease mechanisms. Additionally, we suggest that the analysis of polygenic risk prediction based on genome-wide association studies (GWAS) could, theoretically, be utilized when creating iPSC lines as an additional research tool to identify women who are genetically susceptible to PCOS. Taken together, iPSCPCOS may provide a new paradigm for the exploration of PCOS tissue-specific disease mechanisms.
| S-EPMC10799779 | biostudies-literature
Project description:ObjectiveTo describe the lipidomic characteristics of offspring born to polycystic ovary syndrome (PCOS) women (PCOS-off) and assess the associations between differential lipids and clinical phenotypes.MethodsUltra performance liquid chromatography and mass spectrometry were performed on plasma samples from 70 PCOS-off and 71 healthy controls. The associations of differential metabolites with clinical phenotypes were examined by multiple linear regression.ResultsForty-four metabolites were significantly altered in PCOS-off, including 8 increased and 36 decreased. After stratification according to sex, 44 metabolites (13 increased and 31 decreased) were expressed differently in girls born to PCOS women (PCOS-g), most of which were glycerolipids. Furthermore, 46 metabolites (9 increased and 35 decreased) were expressed differently in boys born to PCOS women (PCOS-b), most of which were glycerophospholipids. Significant associations of metabolites with weight Z-score and high density lipoprotein cholesterol were found in PCOS-off. Triglycerides, low density lipoprotein cholesterol, and thyroid-stimulating hormone were separately correlated with some lipids in PCOS-g and PCOS-b.ConclusionsPCOS-off showed specific lipid profile alterations. The abnormal level of glycerophospholipids and sphingomyelin indicated the risk of glucose metabolism and cardiovascular diseases in PCOS-off. Some lipids, such as phosphatidylcholines, lysophosphatidylcholine and sphingomyelin, may be the potential markers. The results broadened our understanding of PCOS-offs' cardiometabolic status and emphasized more specific and detailed monitoring and management in this population.
| S-EPMC8380809 | biostudies-literature
Project description:To explore the molecular mechanisms of obesity and insulin resistance in the patients with polycystic ovary syndrome (PCOS) at the level of human embryonic stem cells (hESCs).Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.There were 153 differential genes. Of the 153 genes, 91 genes were up-regulated and 62 down-regulated. Nuclear receptor subfamily 0, group B, member 2 (NR0B2) was an up-regulated gene, and GeneChip software system indicated that it was associated with obesity and diabetes. Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.
2013-11-22 | E-GEOD-52422 | biostudies-arrayexpress
Project description:To explore the molecular mechanisms of obesity and insulin resistance in the patients with polycystic ovary syndrome (PCOS) at the level of human embryonic stem cells (hESCs).Three PCOS-derived and one non-PCOS-derived hESC lines were induced into adipocytes, and then total mRNA was extracted from these adipocytes. The differential genes between PCOS-derived and non-PCOS-derived adipocytes were identified with GeneChip, and then were validated with real-time PCR.There were 153 differential genes. Of the 153 genes, 91 genes were up-regulated and 62 down-regulated. Nuclear receptor subfamily 0, group B, member 2 (NR0B2) was an up-regulated gene, and GeneChip software system indicated that it was associated with obesity and diabetes.
2013-11-22 | GSE52422 | GEO
Project description:BackgroundPolycystic ovary syndrome (PCOS) is a kind of endocrine and metabolic disorder, disturbing the females of reproductive age. Here, we aimed to investigate the metabolic characteristics of overweight women with PCOS and analyze the possible mechanisms.MethodsWe conducted a cross-sectional study on 947 patients with PCOS, who were classified according to body mass index (BMI) as overweight (BMI ≥ 24 kg/m2) or non-overweight (BMI ≤ 23.9 kg/m2). The clinical symptoms, endocrine features, metabolic status, and inflammatory levels of the patients were comprehensively assessed and compared between the patients of the two groups. Additionally, a predictive study on the correlation between inflammation and metabolism was performed using STRING and Cytoscape software, and the possible mechanisms of metabolic disorders involved in the overweight PCOS were preliminarily explored.ResultsOverweight PCOS was associated with increased average age, waist-to-hip ratio, and the incidence of acanthosis nigricans. These patients were susceptible to familial hypertension and diabetes, and exhibited evident characteristics of low levels of luteinizing hormone (LH) and the ratio of LH to follicle-stimulating hormone, and were more inclined to insulin resistance (IR). Furthermore, overweight PCOS presented with a chronic low-grade inflammation state with increased levels of inflammatory cytokines complement components C5/C5α, CXCL12/SDF-1, MIF, and Serpin E1/PAI-1 evidently compared with those in non-overweight PCOS. Pearson analysis showed that these inflammatory cytokines were directly or indirectly correlated with IR. The STRING and Cytoscape network analysis predicted that inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1 and MIF might be crucial for inducing IR in overweight PCOS women through various biological functions and signal transductions including the JAK-STAT cascade, ATP biosynthesis, and HIF-1 signaling.ConclusionsOverweight patients with PCOS are prone to low gonadal levels, IR, and chronic low-grade inflammation. Inflammatory cytokines CXCL12/SDF-1, Serpin E1/PAI-1and MIF might lead to IR through multiple biological functions and signal transductions in overweight PCOS.
| S-EPMC9878688 | biostudies-literature
Project description:IntroductionPolycystic ovary syndrome (PCOS) is a common condition characterized by reproductive, hyperandrogenic and dysmetabolic features, and often becomes clinically manifest during adolescence, particularly with weight-gain.Sources of dataPubmed search.Areas of agreementPCOS is heritable and closely associates with obesity (based on data from both epidemiological and genetic studies). Furthermore, insulin resistance forms a central cornerstone of the pathogenesis of PCOS and mediates a close association between obesity and the severity of the phenotypic features of PCOS.Areas of controversyOur understanding of the pathogenesis of PCOS remains incomplete, especially regarding its missing heritability (with only a small fraction having been identified from the genome-wide association studies reported to date), and its developmental origins.Growing pointsA challenge for the future is to explore a role for epigenetic modifications in the development of PCOS, and implications for the in utero environment and novel therapeutic opportunities.
| S-EPMC9494255 | biostudies-literature
Project description:BackgroundThis multi-center, cross-sectional study intended to explore the prevalence and risk factors of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with polycystic ovary syndrome (PCOS).MethodsPatients who met the PCOS Rotterdam diagnostic criteria were enrolled in 6 centers in China, and age-matched healthy volunteers were also recruited. Data were collected including medical history, physical characteristics, and blood tests (liver function, blood lipids, blood glucose and insulin, sex hormones, etc.). Transvaginal or transrectal ultrasound was employed to identify polycystic ovarian morphology (PCOM). The serological score Liver Fat Score (LFS) >-0.640 was used for the diagnosis of NAFLD, and the diagnosis of MAFLD was made according to the 2020 new definition.ResultsA total of 217 PCOS patients and 72 healthy controls were included. PCOS patients had impaired glucose and lipid metabolism, higher liver enzymes and LFS. Both NAFLD (33.6%) and MAFLD (42.8%) was more prevalent in PCOS patients than in controls (4.2%, P < 0.001). Logistic regression results showed that HOMA-IR ≥ 3.54 and ALT ≥ 18.2 were independently associated with NAFLD (P < 0.001) and MAFLD (P ≤ 0.001). The prevalence of NAFLD was significantly higher in PCOS patients with free androgen index (FAI) > 8 (53.8% versus 17.4%, P < 0.001) and BMI ≥ 24 kg/m2 (57.3%, 11.3%, P < 0.001).ConclusionThe prevalence of NAFLD/MAFLD in PCOS patients was significantly higher than that in healthy controls and was independently associated with HOMA-IR and ALT. PCOS patients with overweight and elevated FAI have a higher prevalence of fatty liver.
| S-EPMC10521461 | biostudies-literature