New insights into the genic and metabolic characteristics of induced pluripotent stem cells from polycystic ovary syndrome women

Adult 0301 basic medicine Medicine (General) Granulosa Cells Reverse Transcriptase Polymerase Chain Reaction Research Induced Pluripotent Stem Cells Cell Differentiation QD415-436 Fibroblasts Biochemistry Mitochondria 3. Good health Induced pluripotent stem cells 03 medical and health sciences Metabolism R5-920 PCOS RNA microarray Humans Female Cells, Cultured Polycystic Ovary Syndrome
DOI: 10.1186/s13287-018-0950-x Publication Date: 2018-08-09T09:32:14Z
ABSTRACT
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects female fertility. However, with the lack of corresponding research model, pathology mechanism PCOS poorly understood. Induced pluripotent stem cell (iPSC) technology has been recognized as means to generate patient-specific cells for disease modeling. The mRNA abundance iPSCs was analyzed by RNA microarray real-time polymerase chain reaction (RT-PCR). Karyotyping performed cytogenetic analysis. mitochondrial respiration ability glycolytic function were measured Seahorse Bioscience XF extracellular flux analyzer. expression iPSC-associated markers identified immunofluorescence RT-PCR. teratoma formation studied using immunochemistry. A patient-derived iPSC model established from somatic patients. Through comprehensive transcriptional profiling analysis microarray, showed abnormalities dysfunction compared non-PCOS in vitro. Specifically, total 2904 genes differentially expressed between two populations, which 1416 upregulated 1488 downregulated (fold change > 2, p < 0.01). Gene Ontology (GO) term enrichment results enriched processes activities participated tricarboxylic acid (TCA) cycle, respiratory electron transport (ETC), glycogenolysis. On other hand, related communication, glucose transport, uptake. verified RT-PCR granulosa demonstrated decreased (p 0.05) but increased copy numbers biogenesis 0.05). Subsequently, some metabolism rescued treating metformin iPSCs. Meanwhile, ATP production mitochondria glycolysis also partially returned normal levels. had little effect on maximal capacity. We differences women without gene transcription function. abnormal study provides novel vitro studying clinical causes molecular mechanisms PCOS.
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