Dataset Information

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

ABSTRACT:

Context

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders.

Objective

The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) by analyzing expression profiles with a pathway-oriented method.

Design

Microarrays, RT-PCR, laser capture microdissection, and immunohistochemistry were performed with endometrial tissues.

Setting

This study was performed at a university hospital laboratory.

Patients

This study comprised 12 regularly cycling women and 12 PCOS patients.

Main outcome measure

Dysregulated signaling pathways in PCOSE were identified as a gene set.

Results

Hierarchical clustering revealed distinct expression profiles for PCOSE and the endometrium of normal cycling women. Gene sets associated with androgen signaling were not enriched in PCOSE, although they affect ovarian physiology of PCOS patients. Several biological pathways including cell cycle, apoptosis, glycolysis, and integrin-Rho-cytoskeleton network were aberrantly down-regulated in PCOSE. Expression of genes constituting these gene sets enriched in normal cycling women was systemically down-regulated in PCOSE. Laser capture microdissection-coupled real-time RT-PCR and immunohistochemistry further demonstrated that cell proliferation in the stroma, but not the epithelium, is significantly reduced in PCOSE.

Conclusions

Systemic down-regulation of various signaling pathways in PCOSE with extremely prolonged proliferative phase provides insight into the abnormal phenotypes that reflect pathophysiology of PCOS in the endometrium, possibly leading to increased risks of endometrial disorders.

SUBMITTER: Kim JY

PROVIDER: S-EPMC2682468 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

Kim Jin Yeong JY Song Haengseok H Kim Hyunjoo H Kang Hee Jung HJ Jun Jin Hyun JH Hong Sung Ran SR Koong Mi Kyoung MK Kim In Sun IS

The Journal of clinical endocrinology and metabolism 20090113 4

<h4>Context</h4>Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by chronic oligo/anovulation, hyperandrogenemia, infertility, and metabolic alterations related to insulin resistance. These abnormalities in PCOS may have complex effects on pathophysiology of the endometrium, contributing to infertility and endometrial disorders.<h4>Objective</h4>The objective of this study was to examine dysregulated signaling pathways in the endometrium of patients with PCOS (PCOSE) ...[more]

PMID: 19141577

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Project description:IntroductionAtaxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy.MethodsParticipants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features.ResultsPeople with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls.ConclusionUsing a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.

Project description:ImportanceThe prevalence of polycystic ovary syndrome (PCOS) varies across the globe. Indian studies on PCOS are limited by poor design, small sizes, regional representations, and varying methods.ObjectivesTo estimate the nationwide prevalence of PCOS in India, examine the phenotypic spectrum, and assess the magnitude of comorbidities associated with PCOS.Design, setting, and participantsThis cross-sectional study recruited 9824 women aged 18 to 40 years from November 1, 2018, to July 31, 2022, across 5 zones of the country. A prevalidated questionnaire dichotomized women into screen-positive and screen-negative groups. Relevant clinical, hormonal, and sonographic assessments categorized women as either women with criteria-based PCOS (ie, National Institutes of Health [NIH] 1990 criteria, Rotterdam 2003 criteria, or Androgen Excess and Polycystic Ovary Syndrome Society [AE-PCOS] criteria), women with partial phenotypes (hyperandrogenism, oligomenorrhea, or polycystic morphology labeled as pre-PCOS), or healthy women, in addition to quantitating various comorbidities.Main outcomes and measuresThe prevalence and phenotypes of PCOS among women of reproductive age and the burden of comorbidities associated with PCOS.ResultsA total of 8993 women (mean [SD] age, 29.5 [6.2] years) were enrolled in this study; 196 women were already diagnosed with PCOS, 2251 were categorized as screen positive, and 6546 were categorized as screen negative. The mean (SD) age of screen-positive women (28.1 [6.4] years) was lower than that of screen-negative women (29.7 [6.1] years) (P < .001), and the mean (SD) age at menarche was higher in the former group (13.2 [1.3] vs 13.1 [1.2] years; P < .001). The national prevalence of PCOS was 7.2% (95% CI, 4.8%-10.8%) by NIH 1990 criteria, 19.6% (95% CI, 12.7%-29.2%) by Rotterdam 2003 criteria, and 13.6% (95% CI, 8.4%-21.6%) by AE-PCOS criteria. Overall, PCOS phenotypes C (501 [40.8%]) and D (301 [24.6%]) were the most common, and 492 women (pre-PCOS subgroup) had oligomenorrhea (n = 75), hyperandrogenism (n = 257), or polycystic ovarian morphology (n = 160) only. Among women with PCOS (n = 1224), obesity was present in 529 (43.2%), dyslipidemia in 1126 (91.9%), nonalcoholic fatty liver disease in 403 (32.9%), metabolic syndrome in 305 (24.9%), impaired glucose tolerance in 111 (9.1%), diabetes in 41 (3.3%), and hypertension in 101 (8.3%). The pre-PCOS subgroup (n = 492) displayed similar metabolic aberrations (dyslipidemia: 390 [79.3%]; metabolic syndrome: 78 [15.9%]; nonalcoholic fatty liver disease: 163 [33.1%]; impaired glucose tolerance: 62 [12.6%]; diabetes: 7 [1.4%]; and hypertension: 26 [5.3%]).Conclusions and relevanceIn this cross-sectional study of reproductive-age women recruited across India, the prevalence of PCOS was high, with phenotype C being predominant. Most of these women had metabolic abnormalities. These findings are crucial for developing preventive and therapeutic strategies, potentially integrating PCOS management into national health programs.

Project description:BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied with an increased risk of developing type 2 diabetes mellitus and cardiovascular disease; despite being a common condition, the pathogenesis of PCOS remains unclear. Our aim was to investigate the potential metabolic profiles for different phenotypes of PCOS, as well as for the early prognosis of complications.MethodsA total of 217 women with PCOS and 48 healthy women as normal controls were studied. Plasma samples of subjects were tested using two different analytical platforms of metabolomics: 1H nuclear magnetic resonance (NMR) and gas chromatography/time-of-flight mass spectrometry (GC/TOF-MS).ResultsOur results showed that carbohydrate, lipid and amino acid metabolisms were influenced in PCOS. The levels of lactate, long-chain fatty acids, triglyceride and very low-density lipoprotein were elevated, while glucose, phosphatidylcholine and high-density lipoprotein (HDL) concentrations were reduced in PCOS patients as compared with controls. Additionally, the levels of alanine, valine, serine, threonine, ornithine, phenylalanine, tyrosine and tryptophan were generally increased, whereas the levels of glycine and proline were significantly reduced in PCOS samples compared to controls. Furthermore, the ratio of branched-chain amino acid to aromatic amino acid concentrations (BCAA/AAA) in PCOS plasma was significantly reduced in PCOS patients and was insusceptible to obesity and insulin sensitivity.ConclusionsOur results suggested that the enhanced glycolysis and inhibited tricarboxylic acid cycle (TAC) in women with PCOS. Decrease of BCAA/AAA ratio was directly correlated with the development of PCOS. Ovulatory dysfunction of PCOS patients was associated with raised production of serine, threonine, phenylalanine, tyrosine and ornithine. Elevated levels of valine and leucine, and decreased concentrations of glycine in PCOS plasma could contribute to insulin sensitivity and could be considered as the potential biomarkers for long-term risk assessment of diabetes mellitus.

Dataset Information

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

Context

Objective

Design

Setting

Patients

Main outcome measure

Results

Conclusions

Publications

Transcriptional profiling with a pathway-oriented analysis identifies dysregulated molecular phenotypes in the endometrium of patients with polycystic ovary syndrome.

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