Biomarker For Polycystic Ovary Syndrome Research Articles

Circulating miRNAs in Women with Polycystic Ovary Syndrome: A Longitudinal Cohort Study.

Women with polycystic ovary syndrome (PCOS) often change their metabolic profile over time to decrease levels of androgens while often gaining a propensity for the development of the metabolic syndrome. Recent discoveries indicate that microRNAs (miRNAs) play a role in the development of PCOS and constitute potential biomarkers for PCOS. We aimed to identify miRNAs associated with the development of an impaired metabolic profile in women with PCOS, in a follow-up study, compared with women without PCOS. Clinical measurements of PCOS status and metabolic disease were obtained twice 6 years apart in a cohort of 46 women with PCOS and nine controls. All participants were evaluated for degree of metabolic disease (hypertension, dyslipidemia, central obesity, and impaired glucose tolerance). MiRNA levels were measured using Taqman® Array cards of 96 pre-selected miRNAs associated with PCOS and/or metabolic disease. Women with PCOS decreased their levels of androgens during follow-up. Twenty-six of the miRNAs were significantly changed in circulation in women with PCOS during the follow-up, and twenty-four of them had decreased, while levels did not change in the control group. Four miRNAs were significantly different at baseline between healthy controls and women with PCOS; miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p, which were decreased in PCOS. After follow-up, miR-28-3p, miR-139-5p, and miR-376a-3p increased in PCOS women to the levels observed in healthy controls. Of these, miR-139-5p correlated with total testosterone levels (rho = 0.50, padj = 0.013), while miR-376-3p correlated significantly with the waist-hip ratio at follow-up (rho = 0.43, padj = 0.01). Predicted targets of miR-103-3p, miR-139-5p, miR-28-3p, and miR-376a-3p were enriched in pathways associated with Insulin/IGF signaling, interleukin signaling, the GNRH receptor pathways, and other signaling pathways. MiRNAs altered during follow-up in PCOS patients were enriched in pathways related to immune regulation, gonadotropin-releasing hormone signaling, tyrosine kinase signaling, and WNT signaling. These studies indicate that miRNAs associated with PCOS and androgen metabolism overall decrease during a 6-year follow-up, reflecting the phenotypic change in PCOS individuals towards a less hyperandrogenic profile.

Validation of circulating microRNAs miR-142-3p and miR-598-3p in women with polycystic ovary syndrome as potential diagnostic markers.

Circulating miRNAs previously associated with androgen excess in women might be used as diagnostic biomarkers for polycystic ovary syndrome (PCOS). Models based on circulating miR-142-3p and miR-598-3p expression show good discrimination among women with and without PCOS, particularly when coupled with easily available measurements such as waist-to-hip ratio (WHR) and circulating LH-to-FSH (LH/FSH) ratios. The lack of standardization of the signs, methods, and threshold values used to establish the presence of the diagnostic criteria (hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology) complicates the diagnosis of PCOS. Certain biomarkers may help with such a diagnosis. We conducted a validation study to check the diagnostic accuracy for PCOS of several miRNAs that were associated with the syndrome in a small pilot study that had been previously carried out by our research group. This was a diagnostic test study involving 140 premenopausal women. We included 71 women with PCOS and 69 healthy control women in the study. Both groups were selected as to be similar in terms of body mass index. We used miRCURY LNA™ Universal RT microRNA PCR to analyse the five miRNAs that had shown the strongest associations with PCOS in a much smaller pilot study previously conducted by our group. We studied diagnostic accuracy using receiver operating characteristics (ROC) curve analysis. Only the expression of two miRNAs, miR-142-3p and miR-598-3p, of the five studied, was different between the women with PCOS and the non-hyperandrogenic controls. The diagnostic accuracy of the combination of these circulating miRNAs was good (area under the ROC curve (AUC) 0.801; 95% CI: 0.72-0.88) and was further improved when adding WHR (AUC 0.834, 95% CI: 0.756-0.912), LH/FSH ratio (AUC = 0.869, 95% CI: 0.804-0.934) or both (AUC = 0.895, 95% CI: 0.835-0.954). We developed several models by selecting different threshold values for these variables favouring either sensitivity or specificity, with positive and negative predictive values as high as 88% or 85%, respectively. Patients included here had the classic PCOS phenotype, consisting of hyperandrogenism and ovulatory dysfunction; hence, the present results might not apply to milder phenotypes lacking androgen excess. If confirmed in larger studies addressing different populations and PCOS phenotypes, these biomarkers may be useful to simplify the clinical diagnosis of this prevalent syndrome. This research was funded by Instituto de Salud Carlos III, Spanish Ministry of Science and Innovation (grants PI15/01686, PIE16/00050, PI18/01122 & PI21/00116) and co-funded by European Regional Development Fund 'A way to make Europe'. Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM) and Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS) are also initiatives of the Instituto de Salud Carlos III. The authors have no competing interests to disclose. N/A.

Galectin-1 as a potential diagnostic biomarker in polycystic ovary syndrome.

This study was aimed at comparing the routine laboratory parameters and Galectin-1 levels of control and polycystic ovarian syndrome patients. 88 patients diagnosed with polycystic ovary syndrome and 88 healthy controls were considered for the study. Age groups of the patients ranged from 18 to 40. Serum TSH, Beta HCG, glucose, insulin, HOMA-IR, Hb1A1c, triglyceride, total cholesterol, LDL FSH, LH, E2, prolactin, testosterone, SHBG, DHESO4, HDL, Gal-1 levels were analyzed for each subject. FSH, LH, LH/FSH, E2, prolactin, testosterone, SHBG, DHESO4, HDL and Gal-1 values of the subjects included in the study were statistically significantly different between the groups (p<0.05). Gal-1 and DHESO4 showed a strong positive connection (p=0.05). The sensitivity of Gal-1 level in PCOS patients was calculated as 0.997 and specificity as 0.716. High levels of Gal-1 in PCOS patients suggest that it increases due to overexpression in response to inflammation.

Serum anti-Müllerian hormone: A potential biomarker for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by chronic ovulatory dysfunction, hyperandrogenism and polycystic ovary morphology (PCOM). Although hyperandrogenism is one of the major features of PCOS, it is rarely observed in southeast Asia. Recently, however, there has been growing evidence on association of anti-Müllerian hormone (AMH) with PCOS. The objective of this study was to investigate the diagnostic potentials of AMH in PCOS individuals. This case-control study included a total of 131 women with PCOS and 49 healthy controls who were enrolled after the exclusion of secondary causes of PCOS. Serum AMH was measured using an ultra-sensitive AMH ELISA kit in addition to other diagnostic biomarkers. Statistical analyses was carried out using the Student's t test, Wilcoxon rank-sum test, receiver operating characteristic (ROC) curve analysis, Spearman's rank correlation test and multivariable binary logistic regression analysis. The median AMH values were 8.5 ng/ml and 2.5 ng/ml in the study group and controls, respectively ( P <0.001). The normal cutoff value of 4.1 ng/ml for AMH was derived from ROC curve analysis. With a 4.1 ng/ml cut-off value, high levels of AMH was found in about 84 per cent of PCOS cases. However, no significant difference in AMH level was noted between age groups (<20 vs . ≥20 yr), body mass index (BMI) (<25 vs . ≥25 kg/m 2 ) and PCOM types. The area under the ROC curve (AUC) for AMH yielded diagnostic range values. In total PCOS cases, AUC was 0.93 (95% CI: 0.88 and 0.96), and in phenotype A PCOS cases, AUC was 0.96 (95% CI: 0.91 and 0.98). The correlation test also showed no association with BMI, the FG score, PCOM, free androgen index, androstenedione, dehydroepiandrosterone sulphate and luteinizing hormone. However, a weak correlation was observed with testosterone in total PCOS cases and with DHT as well as age in phenotype A PCOS cases. The prediction model for PCOS using multivariable binary logistic regression analysis showed AMH as the best marker. The results of this study suggest that AMH can be considered as the most promising biomarker in PCOS women, particularly with phenotype A and phenotype D.

Screening and verification of genes related to polycystic ovary syndrome

To identify key genes involved in occurrence and development of polycystic ovary syndrome (PCOS). By downloading the GSE85932 dataset from the GEO database, we used bioinformatical analysis to analyse differentially expressed genes (DEGs) from blood samples of eight women with PCOS and eight matched controls. Following bioinformatic analysis, we performed a cross-sectional study of serum samples taken from 79 women with PCOS and 36 healthy controls. From the 178 DEGs identified by bioinformatical analysis, 15 genes were identified as significant, and of these, ORM1 and ORM2 were selected for further verification as potential biomarkers for PCOS. Serum ORM1 and ORM2 levels were significantly increased in women with PCOS, and had a high diagnostic value. ORM1 and ORM2 were positively correlated with testosterone, cholesterol, and triglycerides. ORM1 levels were negatively correlated with high density lipoprotein (HDL) while ORM2 levels showed no significant correlation. ORM may be an effective biomarker for the diagnosis of PCOS and its monitoring may be a useful therapeutic strategy.

A PPARG Splice Variant in Granulosa Cells Is Associated with Polycystic Ovary Syndrome.

We explored whether there are splice variants (SVs) of peroxisome proliferator-activated receptor-gamma (PPARG) in polycystic ovary syndrome (PCOS) patients and its relationship with clinical features and KGN cell functions. We performed a study involving 153 women with PCOS and 153 age-matched controls. One type of PPARG SV was detected by SMARTer RACE. The correlations between PPARG SV expression levels, clinical features, and KGN cell functions were analyzed. The effect of the PPARG SV on the expression of important genes in metabolism-related pathways was explored by PCR array. The expression of the PPARG SV in PCOS patients was significantly higher than that in the controls. Clinical features were more significant in the PCOS group with the SV. Compared with overexpression of PPARG, the overexpression of the PPARG SV inhibited the proliferation, migration, and apoptosis of KGN cells in vitro. The genes related to the PPARG SV were mainly involved in lipid metabolism. While granulosa cells contribute greatly to the development of follicles, our results suggest that the identified PPARG SV may regulate cell proliferation, migration, and apoptosis in granulosa cells, which could partially explain the mechanisms of ovulation dysfunction in PCOS. Further investigation of the utility of this PPARG SV as a biomarker for PCOS is warranted.

Identifying miRNA biomarkers of polycystic ovary syndrome through text mining

Objective: Polycystic ovary syndrome (PCOS) is an endocrine disorder with diverse clinical manifestations that often occurs in women of childbearing age. However, its molecular pathogenesis remains unclear, and this study aimed to identify miRNA targets in PCOS through text mining and database analysis. Methods: First, three different sets of text mining genes (TMGs) associated with “polycystic ovary syndrome”, “obesity/adiposis”, and “anovulation” keywords were retrieved from the GenCLiP3 database, and overlapping genes were selected. Second, Gene ontology annotation and biological pathway enrichment analyses of these overlapping TMGs were performed, followed by protein–protein interaction (PPI) network analysis. Third, genes in the gene module clustered in the PPI were selected to predict potential miRNAs for PCOS via miRNA-mRNA analysis. Results: A total of 4291 TMGs related to three different keywords were obtained through text mining; 72 intersect TMGs were retained among the three gene sets, and 62 TMGs participated in the establishment of the PPI network, of which 18 were aggregated in the gene module. Finally, 11 miRNAs that simultaneously bound to two TMGs (IGF1, ESR1, MAPK1, NAMPT, PIK3CA, and SERPINE1) could be prioritized as targets to study PCOS. Conclusion(s): The discovery of 11 miRNAs (miR-301a-3p, miR-301b-3p, miR-3666, miR-454-3p, miR-130a-3p, miR-130b-3p, miR-4295, miR-190a-3p, miR-5011-5p, miR-548c-3p, and miR-4799-5p) and 6 TMGs, which are associated with the HIF-1 signaling pathway (P = 4.799E-08), could be used as potential targets for PCOS.

Evaluation of circulating microRNA profiles in Brazilian women with polycystic ovary syndrome: A preliminary study.

ObjectivePolycystic ovary syndrome (PCOS) is a heterogeneous endocrinopathy, which etiology encompasses complex genetic traits associated with epigenetic factors, including differences in microRNA (miRNA) expression in a variety of tissues. The circulating form of these molecules is raising attention in the syndrome not only as potential biomarkers of PCOS but also as possible therapeutic targets. The aim of this study was to explore the circulating miRNA profiles present in a cohort of Brazilian women with and without PCOS and to evaluate the potential role of miRNAs in the pathophysiology of the syndrome.MethodsCross-sectional study of 36 well-characterized PCOS women and 16 healthy controls. Clinical, hormone and metabolic data were recorded and evaluated. The expression profile of the 201 circulating miRNA selected were analyzed by taqman quantitative real time polymerase chain reactions (RT-PCR) using a customized Open Array platform. Statistical and bioinformatic analyzed were performed.ResultsCirculating miR-21-5p, miR-23a-3p and miR-26a-5p were upregulated, and miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p were downregulated in women with PCOS compared to healthy normo-ovulatory controls. miR-21-5p, miR-103a-3p and miR-376a-3p levels correlated positively with androgen levels. These miRNAs, in combination, were related to pathways involved in insulin signaling, steroids biosynthesis and endothelial regulation as well as in folliculogenesis.ConclusionIn this study, we identified a specific circulating miRNA signature in Brazilian women with PCOS. According to our data, circulating miR-21-5p, miR-23a-3p, miR-26a-5p, miR-103a-3p, miR-376a-3p, miR-19b-3p and miR-222-3p may represent potential candidates for differential diagnosis of PCOS in the future.

Follicular fluid lipidomic profiling reveals potential biomarkers of polycystic ovary syndrome: A pilot study.

BackgroundPolycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with multiple metabolic conditions including obesity, insulin resistance, and dyslipidemia. PCOS is the most common cause of anovulatory infertility; however, the molecular diversity of the ovarian follicle microenvironment is not fully understood. This study aimed to investigate the follicular fluid (FF) lipidomic profiles in different phenotypes of PCOS and to explore novel lipid biomarkers.MethodsA total of 25 women with PCOS and 12 women without PCOS who underwent in vitro fertilization and embryo transfer were recruited, and their FF samples were collected for the lipidomic study. Liquid chromatography-tandem mass spectrometry was used to compare the differential abundance of FF lipids between patients with different PCOS phenotypes and controls. Subsequently, correlations between specific lipid concentrations in FF and high-quality embryo rate (HQER) were analyzed to further evaluate the potential interferences of lipid levels with oocyte quality in PCOS. Candidate biomarkers were then compared via receiver operating characteristic (ROC) curve analysis.ResultsIn total, 19 lipids were identified in ovarian FF. Of these, the concentrations of ceramide (Cer) and free fatty acids (FFA) in FF were significantly increased, whereas those of lysophosphatidylglycerol (LPG) were reduced in women with PCOS compared to controls, especially in obese and insulin-resistant groups. In addition, six subclasses of ceramide, FFA, and LPG were correlated with oocyte quality. Twenty-three lipid subclasses were identified as potential biomarkers of PCOS, and ROC analysis indicated the prognostic value of Cer,36:1;2, FFA C14:1, and LPG,18:0 on HQER in patients with PCOS.ConclusionsOur study showed the unique lipidomic profiles in FF from women with PCOS. Moreover, it provided metabolic signatures as well as candidate biomarkers that help to better understand the pathogenesis of PCOS.

Identification of novel candidate biomarkers and immune infiltration in polycystic ovary syndrome

BackgroundIn this study, we aimed to identify novel biomarkers for polycystic ovary syndrome (PCOS) and analyze their potential roles in immune infiltration during PCOS pathogenesis.MethodsFive datasets, namely GSE137684, GSE80432, GSE114419, GSE138518, and GSE155489, were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were selected from the train datasets. The least absolute shrinkage and selection operator logistic regression model and support vector machine-recursive feature elimination algorithm were combined to screen potential biomarkers. The test datasets validated the expression levels of these biomarkers, and the area under the curve (AUC) was calculated to analyze their diagnostic value. Quantitative real-time PCR was conducted to verify biomarkers’ expression in clinical samples. CIBERSORT was used to assess differential immune infiltration, and the correlations of biomarkers with infiltrating immune cells were evaluated.ResultsHerein, 1265 DEGs were identified between PCOS and control groups. The gene sets related to immune response and adaptive immune response were differentially activated in PCOS. The two diagnostic biomarkers of PCOS identified by us were HD domain containing 3 (HDDC3) and syndecan 2 (SDC2; AUC, 0.918 and 0.816, respectively). The validation of hub biomarkers in clinical samples using RT-qPCR was consistent with bioinformatics results. Immune infiltration analysis indicated that decreased activated mast cells (P = 0.033) and increased eosinophils (P = 0.040) may be a part of the pathogenesis of PCOS. HDDC3 was positively correlated with T regulatory cells (P = 0.0064), activated mast cells (P = 0.014), and monocytes (P = 0.024) but negatively correlated with activated memory CD4 T cells (P = 0.016) in PCOS. In addition, SDC2 was positively correlated with activated mast cells (P = 0.0021), plasma cells (P = 0.0051), and M2 macrophages (P = 0.038) but negatively correlated with eosinophils (P = 0.01) and neutrophils (P = 0.031) in PCOS.ConclusionHDDC3 and SDC2 can serve as candidate biomarkers of PCOS and provide new insights into the molecular mechanisms of immune regulation in PCOS.

Serum fibrinogen-like protein 1 as a novel biomarker in polycystic ovary syndrome: a case-control study.

To investigate the relationship between fibrinogen-like protein 1 (FGL-1) concentrations and various metabolic characteristics in patients with polycystic ovary syndrome (PCOS) and explore whether FGL-1 could be a predictive biomarker for PCOS. This case-control study included 136 patients with PCOS and 34 normal controls recruited in the Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital between May 2017 and June 2021. Anthropometric characteristics, metabolic parameters, and reproductive hormones were collected. Serum FGL-1 measurement was conducted using enzyme-linked immunosorbent assay (ELISA) kits. Serum FGL-1 concentrations were higher in patients with PCOS than in control subjects in body mass index (BMI) subgroups, insulin resistance (IR) subgroups, and hepatic function subgroups, respectively. Serum FGL-1 concentrations were significantly associated with BMI, glycosylated hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), alanine aminotransferase (ALT), aspartate aminotransferase (AST), high-density lipoprotein cholesterol (HDL-c), and serum uric acid (SUA) in all individuals. The receiver operating characteristic (ROC) curve analysis revealed that the best cutoff value for FGL-1 levels to predict PCOS was 21.02ng/ml with a sensitivity of 74.3% and a specificity of 70.6%. Both univariate and multiple logistic regressions indicated that the odds ratio (OR) for PCOS significantly increased in the subjects with high levels of FGL-1. In our study, FGL-1 was associated with serum aminotransferase and various metabolic indexes. Moreover, the high risk of PCOS was independently associated with the increased FGL-1 levels, which suggested that FGL-1 could be a predictive biomarker for PCOS.

TO ASSESS ROLE OF C-REACTIVE PROTEIN TO ALBUMIN RATIO AS A NEW BIOMARKER FOR POLYCYSTIC OVARY SYNDROME

Women with Polycystic Ovary Syndrome (PCOS) are found to have greater chronic subclinical inammation.CRP/albumin ratio is a marker for inammation related to metabolic dysfunction The aim of the study was to assess role of C-reactive protein to albumin ratio as a new biomarker for polycystic ovary syndrome.45 women fullling Rotterdam criteria for diagnosis of PCOS were selected.Inammatory markers - Procalcitonin, Interleukin 6, C-reactive protein (CRP) and CRP/albumin ratio were measured. Data was analysed and conclusions drawn.CRP/albumin ratio was found to have better sensitivity and lower false positive rates (0.96,0.09) as compared to Interleukin 6 (0.96,0.27), hsCRP (0.93,0.09) and Procalcitonin (0.40,0.13). CRP/albumin ratio may be particularly useful and cost-effective method to assess inammation in women with PCOS,which may help to early diagnose the metabolic effects of PCOS

P-590 Discriminatory value of steroid hormones on polycystic ovary syndrome in women with infertility and obesity

Abstract Study question Which steroid hormone (ratio) has the highest discriminatory value in the biochemical diagnosis of polycystic ovary syndrome (PCOS) in women with infertility and obesity? Summary answer Androstenedione (A4) is a potentially useful discriminatory biomarker for PCOS in women with obesity, whereas Testosterone (T)/Dihydrotestosterone (DHT) and 11-oxygenated androgens are not. What is known already The best biomarker to assess biochemical hyperandrogenism in PCOS is still under discussion. Serum total or free T, followed by Free Androgen Index (FAI), and Dehydroepiandrosterone Sulfate (DHEA-S) are the most widely used biomarkers. T/DHT ratio has been proposed as a useful biomarker for PCOS. Moreover, a recent study demonstrated 11-oxygenated androgens represent the majority of circulating androgens in PCOS. Whether this is also relevant in women with obesity is unclear. We aimed to assess the discriminatory value of different steroid hormones and their ratios for PCOS as well as adverse metabolic phenotype within PCOS in women with obesity. Study design, size, duration We used the baseline data and samples originating from an RCT that examined whether a six-month lifestyle intervention prior infertility treatment in women with obesity improved live birth rate, compared to prompt infertility treatment. In total of 577 women with obesity were randomized between 2009 and 2012. Women were diagnosed with PCOS according to the Rotterdam criteria. Metabolic syndrome was diagnosed based on the revised criteria of the National Cholesterol Education Program. Participants/materials, setting, methods Women with PCOS comprised the study group (N = 132). Ovulatory women with idiopathic, tubal or male factor infertility were the control group (N = 83). Women were excluded when blood sampling was performed in the luteal phase or when baseline samples were unavailable. The steroid hormones were measured using LC-MS/MS. 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) were analyzed using LC-MS/MS in a separate method. The discriminatory value was based on receiver operator characteristic (ROC) curves with adjustment for age. Main results and the role of chance The mean age was 28.1 years in the PCOS group and 30.9 years in the control group (p &amp;lt; 0.001). BMI was not significantly different (36.0±3.2 versus 35.7±3.5, p = 0.51). Among the tested steroid hormones (ratios), SHBG, A4, T, DHT, 11KT, FAI, T/DHT ratio, and T/A4 ratio showed statistically significant differences between the PCOS and the control group. DHEA, DHEA-S, 11OHA4 did not differ between the groups. The crude AUCs of FAI, T, A4, T/DHT ratio, SHBG, 11KT, T/A4 ratio, and DHT in ROC analysis for representing PCOS were 0.85, 0.84, 0.81, 0.70, 0.62, 0.59, 0.58, and 0.57 respectively. Among the markers with crude AUCs≥0.70, the incremental value of the marker A4 (AUC difference: 0.14, 95%CI: 0.07 to 0.21), T (0.18, 95%CI: 0.10 to 0.25), and FAI (0.18, 95%CI: 0.10 to 0.25) in addition to age showed significant improvement, but T/DHT ratio (0.02, 95%CI: –0.01 to 0.04) did not. However, the combination of A4 together with T or FAI did improve discriminatory value of individual T or FAI (AUC difference: –0.001, 95%CI: –0.004 to 0.003 and 0.007, –0.007 to 0.02, respectively). None of the measured steroid hormones (ratios) have promising discriminatory value for adverse metabolic phenotype within PCOS in women with obesity. Limitations, reasons for caution This is a post-hoc analysis and no power calculation was performed. There was a significant difference in age between women with and without PCOS, and residual confounding might exist. All PCOS patients in this analysis were infertile and obese, and it is conceivable that milder PCOS phenotypes are not represented. Wider implications of the findings T/DHT ratio and 11-oxygenated androgens might not serve as a promising discriminatory biomarker for PCOS in women with obesity, nor for adverse metabolic phenotype within PCOS in these women. A4 is a potential biomarker for PCOS diagnosis in women with infertility and obesity, however, its utility potency needs further validation. Trial registration number NTR 1530

MicroRNAs and long non-coding RNAs as biomarkers for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is known as the most common metabolic/endocrine disorder among women of reproductive age. Its complicated causality assessment and diagnostic emphasized the role of non‐coding regulatory RNAs as molecular biomarkers in studying, diagnosing and even as therapeutics of PCOS. This review discusses a comparative summary of research into microRNAs (miRNAs) and long non‐coding RNAs (lncRNAs) that are molecularly or statistically related to PCOS. We categorize the literature in terms of centering on either miRNAs or lncRNAs and discuss the combinatory studies and promising ideas as well. Additionally, we compare the pros and cons of the prominent research methodologies used for each of the abovementioned research themes and discuss how errors can be stopped from propagation by selecting correct methodologies for future research. Finally, it can be concluded that research into miRNAs and lncRNAs has the potential for identifying functional networks of regulation with multiple mRNAs (and hence, functional proteins). This new understanding may eventually afford clinicians to control the molecular course of the pathogenesis better. With further research, RNA (with statistical significance and present in the blood) may be used as biomarkers for the disease, and more possibilities for RNA therapy agents can be identified.

Chemerin regulates autophagy to participate in polycystic ovary syndrome.

ObjectivePolycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. Chemerin has recently been discovered as a novel adipokine associated with obesity and metabolic syndrome. Excessive autophagy activity and overexpression of autophagy-related genes in follicular granulosa cells are important mechanisms of PCOS. This study aimed to investigate the effect of chemerin on autophagy in PCOS.MethodsA rat model of PCOS was established by subcutaneous injection of testosterone propionate under a high-fat diet. Expression levels of chemerin and its receptor CMKLR1 were determined by real-time polymerase chain reaction and western blot. Proliferation and apoptosis of human granulosa cells in vitro and expression of autophagy-related genes were examined using bafilomycin A1 (autophagy inhibitor) and Torin1 (autophagy inducer).ResultsChemerin and CMKLR1 expression were significantly increased in the ovary in a rat model of PCOS. Ectopic expression of chemerin promoted the proliferation and inhibited the apoptosis of COV434 cells. Ectopic expression of chemerin also induced autophagy by inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway.ConclusionsChemerin and CMKLR1 were overexpressed in PCOS rats. Chemerin promoted autophagy through inhibiting the PI3K/Akt/mTOR pathway, and may provide a potential target and biomarker of PCOS.

Association of tumor necrosis factor-α (−308 G/A) and interleukin-10 (−1082 A/G) gene polymorphisms with polycystic ovary syndrome in Iraqi women

BackgroundThe etiologic factors of polycystic ovary syndrome (PCOS) are not well understood, however, several studies reported that genetics and environmental factors might be involved in the appearance of PCOS. Therefore understanding some molecular pathways can provide more information about PCOS. The imbalance of pro-inflammatory and anti-inflammatory cytokines could be associated with its pathophysiology. There are huge numbers of polymorphisms within cytokine genes that may affect their production and bring in the women more susceptible for PCOS. The aim of the present study was for evaluation the correlation of single nucleotide polymorphism (−308 G/A) in tumor necrosis factor-alpha (TNF-α) gene and (−1082 A/G) in interleukin-10 (IL-10) gene with PCOS. MethodsPatients group included 80 women who had a history of PCOS diagnosed using transvaginal or transabdominal ultrasound and don't have any of the inherited disorders such as androgen-secreting neoplasms, congenital adrenal hyperplasia, thyroid dysfunction, and hyperprolactinemia with a mean age (27.23 year). The control group included 70 women with a mean age (26.89 year). Levels of serum IL-10 and TNF-α in woman with PCOS and healthy control have been measured by Enzyme linked immunosorbent assay (ELISA). Single nucleotide polymorphism (SNP) in TNF-α (−308 G/A) and IL-10 (−1082 A/G) genes and the frequency of mutations in patient and control group were evaluated using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). ResultsShowed that serum IL-10 concentration was significantly decreased (p < 0.01) while TNF-α level was significantly increased (p < 0.01) in patients compared to control group. While the genotype prevalence of TNF-α (−308 G/A) and IL-10 (−1082 A/G) and the allele frequency show non-significant difference (p > 0.05) between women with PCOS and healthy controls. ConclusionIt is concluded that the level of TNF–α and IL-10 could be considered as possible biomarkers for PCOS while polymorphisms in IL-10 gene and TNF-α gene are not considered as risk factors of PCOS in Iraqi women, this suggests that further studies on other loci or other cytokines are required.

Identification of Three Potential circRNA Biomarkers of Polycystic Ovary Syndrome by Bioinformatics Analysis and Validation.

ObjectiveIt is well known that circRNAs are closely involved in the progression of various diseases. However, their functions and potential regulatory mechanisms in polycystic ovary syndrome (PCOS) remain largely unknown. In the present study, our aim was to investigate the potential diagnostic value of circRNAs in PCOS.MethodsThe circRNA dataset GSE145296, mRNA dataset GSE155489 and miRNA GSE138572 were downloaded from Gene Expression Omnibus (GEO) database. Then, differentially expressed genes (DEGs) were identified. Based on the potential interactions, a network of cirRNA-related competing endogenous RNAs (ceRNAs) was constructed. Biological functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. For further validation, qRT-PCR method was used to detect the expression level of the candidate circRNAs. Then, receiver operating characteristics (ROC) were constructed to evaluate the diagnostic value of the three differentially expressed circRNA (DE-circRNA).ResultsWe constructed a network of cirRNA-related ceRNA network. Hsa_circ_0075691, hsa_circ_0075692 and hsa_circ_0085997 were validate to be dysregulated in PCOS.ConclusionHsa_circ_0075691, hsa_circ_0075692 and hsa_circ_0085997 may be potential diagnostic biomarkers of PCOS, but their specific regulatory mechanisms still need to be further studied.

Are neutrophil count and neutrophil/lymphocyte ratio useful as markers of polycystic ovary syndrome in early reproductive age?

Necrotizing fasciitis (NF) is often fatal, characterized by extensive necrosis of the subcutaneous tissues and fascia. The present study was aimed to validate the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score as a tool to predict/diagnose NF and to differentiate it from other soft tissue infections depending on the score. A Prospective Observational study was conducted in ESICMC PGI MSR, Medical College Hospital, Rajajinagar, Bengaluru, from Jan 2019 to June 2020. Patients ≥18 years of age with severe soft tissue infections were included in the study. Based on the LRINEC score, the patients were categorised as low (≤5), moderate (6-7) and high risk (≥8) for the prediction of onset or diagnosis of NF. Data analysis was performed using SPSS version 21.0. A total of 55 patients were included in the study. A significant 3 association was observed with age (p=0.042), LRINEC score (p=0.0001), C Reactive Protein (CRP; p=0.0001), haemoglobin (p=0.008), serum Department of XXX, University of XXX, XXX Training and Research Hospital, City, Country sodium levels (p=0.004), serum creatinine (0.001), and amputation (p=0.004). Amputation was done in 5 cases. Only 1 mortality was observed 4Department of XXX, Faculty of XXX, City, Country in LRINEC high risk group with NSSTI. To conclude, LRINEC scoring system showed a better positive predictive value in identifying the onset of NF and risk strategizing of the patients with severe soft tissue infections. This study has aimed to contribute to the literature by investigating the value of inflammatory biomarkers of polycystic ovary syndrome (PCOS) that can be tested via a complete blood count. This retrospectively designed case-control study included 197 women in early reproductive age; who were in the age range of 18-24 years and who were admitted to the gynecology outpatient clinic. A total of 111 PCOS patients; in whom the diagnosis of PCOS was made based on Rotterdam criteria, were included in the study. A control group was formed by including 86 healthy women. All measurements of inflammatory biomarkers were obtained from the complete blood count test results. Of the inflammatory markers; the neutrophil count and the neutrophil/lymphocyte ratio were statistically significantly higher in the PCOS group compared to the control group (p=0.016 and p=0.002, respectively); however, the measured values of other parameters were similar between two groups. To evaluate whether or not the neutrophil count and neutrophil/lymphocyte ratio could be used as a screening tool to exclude PCOS, we constructed a receiver-operating characteristic curve (ROC). The ROC curve for the neutrophil count was 0.60 (p=0.016) and NLR was 0.627 (p=0.002). The neutrophil count and NLR were higher in the PCOS cases compared to the age-matched individuals in the control group. This finding confirms the presence of inflammation in PCOS cases of early reproductive age. However, it has been demonstrated that the diagnostic values of these markers are not strong in distinguishing PCOS patients from healthy individuals.

Sestrin2 and Beclin1 levels in Polycystic Ovary Syndrome.

BackgroundSestrin2 and beclin1 are two newly found proteins that have essential roles in autophagy. This study attempted to evaluate the plasma concentrations of sestrin2 and beclin1 in women with polycystic ovary syndrome (PCOS) and healthy controls and to explore the clinical value of these proteins as novel biomarkers for PCOS.MethodsIn this case‐control study, plasma levels of sestrin2 and beclin1, fasting blood sugar (FBS), lipid profile, insulin, and androgens were evaluated in 63 women (31 patients and 32 controls). Sestrin2 and beclin1 levels were determined using enzyme‐linked immunosorbent assay (ELISA). Descriptive statistics, correlation coefficients, logistic regression, and ROC curve analyses were used in this study.ResultsPlasma sestrin2 levels of the subjects with PCOS (40.74 [24.39–257.70]) were significantly lower than those of healthy subjects (255.78 [25.46–528.66]; p‐value = 0.040). ROC curve analysis showed that a cutoff value of 420.5 ng/L had an appropriate sensitivity (83.87%) and specificity (46.88%) for discriminating individuals with and without PCOS, with the area under the curve (95% CI) of 0.648 (0.518 to 0.764), p = 0.036. There were no statistically significant differences between the two groups concerning plasma levels of beclin1, biochemical parameters, blood pressure, and anthropometric features.ConclusionOur findings highlight the dysregulation of sestrin2 as a marker of autophagy in PCOS and its potential usefulness as a novel biomarker for PCOS. Further research is needed to better understand the role of this protein in the pathophysiology of PCOS and its value as a diagnostic tool for the evaluation of PCOS patients.

Serum Metabolomics in PCOS Women with Different Body Mass Index.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder, affecting 5–10% of women of reproductive age. It results from complex environmental factors, genetic predisposition, hyperinsulinemia, hormonal imbalance, neuroendocrine abnormalities, chronic inflammation, and autoimmune disorders. PCOS impacts menstrual regularities, fertility, and dermatological complications, and may induce metabolic disturbances, diabetes, and coronary heart disease. Comprehensive metabolic profiling of patients with PCOS may be a big step in understanding and treating the disease. The study aimed to search for potential differences in metabolites concentrations among women with PCOS according to different body mass index (BMI) in comparison to healthy controls. We used broad-spectrum targeted metabolomics to evaluate metabolites’ serum concentrations in PCOS patients and compared them with healthy controls. The measurements were performed using high-performance liquid chromatography coupled with the triple quadrupole tandem mass spectrometry technique, which has highly selective multiple reaction monitoring modes. The main differences were found in glycerophospholipid concentrations, with no specific tendency to up-or down-regulation. Insulin resistance and elevated body weight influence acylcarnitine C2 levels more than PCOS itself. Sphingomyelin (SM) C18:1 should be more intensively observed and examined in future studies and maybe serve as one of the PCOS biomarkers. No significant correlations were observed between anthropometric and hormonal parameters and metabolome results.