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Differential Gene Expression in Granulosa Cells from Polycystic Ovary Syndrome Patients with and without Insulin Resistance: Identification of Susceptibility Gene Sets through Network Analysis. Kaur S et al. Context:Polycystic ovary syndrome (PCOS) is a heterogeneous, genetically complex, endocrine disorder of uncertain etiology in women.Objective:Our aim was to compare the gene expression profiles in stimulated granulosa cells of PCOS women with and without insulin resistance vs. matched controls.Research Design and Methods:This study included 12 normal ovulatory women (controls), 12 women with PCOS without evidence for insulin resistance (PCOS non-IR), and 16 women with insulin resistance (PCOS-IR) undergoing in vitro fertilization. Granulosa cell gene expression profiling was accomplished using Affymetrix Human Genome-U133 arrays. Differentially expressed genes were classified according to gene ontology using ingenuity pathway analysis tools. Microarray results for selected genes were confirmed by real-time quantitative PCR.Results:A total of 211 genes were differentially expressed in PCOS non-IR and PCOS-IR granulosa cells (fold change=1.5; P=0.001) vs. matched controls. Diabetes mellitus and inflammation genes were significantly increased in PCOS-IR patients. Real-time quantitative PCR confirmed higher expression of NCF2 (2.13-fold), TCF7L2 (1.92-fold), and SERPINA1 (5.35-fold). Increased expression of inflammation genes ITGAX (3.68-fold) and TAB2 (1.86-fold) was confirmed in PCOS non-IR. Different cardiometabolic disease genes were differentially expressed in the two groups. Decreased expression of CAV1 (-3.58-fold) in PCOS non-IR and SPARC (-1.88-fold) in PCOS-IR was confirmed. Differential expression of genes involved in TGF- signaling (IGF2R, increased; and HAS2, decreased), and oxidative stress (TXNIP, increased) was confirmed in both groupsConclusions:Microarray analysis demonstrated differential expression of genes linked to diabetes mellitus, inflammation, cardiovascular diseases, and infertility in the granulosa cells of PCOS women with and without insulin resistance. Because these dysregulated genes are also involved in oxidative stress, lipid metabolism, and insulin signaling, we hypothesize that these genes may be involved in follicular growth arrest and metabolic disorders associated with the different phenotypes of PCOS.
Aleporou-Marinou V et al 2002 reported the presence of alpha1-antitrypsin and transferrin in human
follicular fluid.
Proteins from human follicular fluid were purified after
ammonium sulfate fractionation followed by water dialysis and High Performance
Liquid Chromatography. The fraction of peak 3 showed a single band on
electrophoresis and its N-terminal amino acid sequence was similar to that of
human serum transferrin. The fraction of peak 10 proved to be a glycoprotein
and its N-terminal amino,acid sequence was similar to that of human serum
alpha1-antitrypsin.
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