Risk Of Polycystic Ovary Syndrome Research Articles

The dietary phytochemical index and its relation to polycystic ovary syndrome: a case-control study.

Polycystic ovary syndrome (PCOS), a hormonal disorder affecting women of reproductive age, can be significantly impacted by diet. This study explores the relationship between a diet rich in phytochemicals, measured by the Dietary Phytochemical Index (DPI), and PCOS, along with associated health markers. A case-control study design was implemented with 480 individuals diagnosed with PCOS based on the Rotterdam criteria, paired with 480 controls matched in terms of age and BMI. The evaluation encompassed dietary intake, anthropometric measurements, and hormonal/metabolic markers. Additionally, the DPI score was determined based on the consumption of phytochemical-rich foods. The study also examined PCOS-related complications like acne and irregular menstrual cycles, as well as mental health using the Beck Depression Inventory (BDI-II) scores. Women with PCOS had significantly lower DPI scores (32.42 vs 43.87, p < 0.001) compared to the control group, indicating a less phytochemical-rich diet. The DPI scores coincided with higher levels of hormones typically associated with PCOS, including Luteinizing Hormone (LH), Dehydroepiandrosterone Sulfate (DHEA-S), and testosterone. Additionally, these scores were associated with markers of metabolic dysfunction such as C-reactive Protein (CRP), Fasting Blood Sugar (FBS), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while positively correlating with Sex Hormone-Binding Globulin (SHBG) (all p < 0.050).). Higher DPI scores were associated with a significantly reduced risk of PCOS (OR: 0.13, 95% CI: 0.08, 0.23, P for trend: 0.001) and its complications, including acne and irregular menstrual cycles. Interestingly, a positive association emerged, suggesting better mental health (lower BDI-II scores) with higher DPI scores. In conclusion, this study indicates that lower DPI scores are associated with a higher incidence and severity of PCOS, suggesting that a phytochemical-rich diet could potentially benefit the management of PCOS by enhancing hormonal profiles, metabolic health, and mental well-being in women.

Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.

Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk. To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis. Cox regression models analysed the association between PCOS and MS risk. The genome-wide cross-trait analysis examined the genetic architecture. In a Swedish cohort of 1,374,529 women, 77 (0.3%) with PCOS and 3,654 (0.3%) without PCOS were diagnosed with MS. After adjusting for birth year and obesity, no association was found between PCOS and MS (HR = 0.91, 95% CI = 0.72-1.15), which was confirmed by Mendelian randomization analysis, where genetically predicted PCOS propensity, sex hormone-binding globulin (SHBG), or testosterone levels did not causally affect MS risk (all p-values > 0.05). By exploring horizontal pleiotropy, we identified shared genetic regions and 19 independent pleiotropic SNPs for SHBG with MS and 11 for testosterone with MS. We did not find evidence for a causal role of PCOS, as a proxy of elevated testosterone, in reducing the risk of MS in women. The shared genetic loci between testosterone, SHBG, and MS provide biological insights.

Causal relationship between inflammatory cytokines and polycystic ovary syndrome: a bidirectional mendelian randomization study.

Polycystic ovary syndrome (PCOS) is defined as a chronic low-grade inflammatory reproductive endocrine disorder. PCOS can induce various metabolic disorders, which are associated with a state of mild and slow-acting inflammation. Nevertheless, the causal relationship between polycystic ovary syndrome and inflammatory factors is uncertain. The causality between inflammatory cytokines and PCOS was analyzed by bidirectional Mendelian randomization (MR) in this current probe. We performed an interactive MR study to assess the causal relationships between 91 inflammatory cytokines and PCOS using Genome Wide Association Study (GWAS) data. We underwent dual-sample MR analysis with inverse variance weights (IVW) as the predominant MR methodology with multiple validity and heterogeneity analyses. MR-Egger, weighted median, simple mode, weighted mode and MR-PRESSO were analyzed as multiple likelihood sensitivity analyses to enhance the final results.The results came out interleukin-1-alpha (IL-1A) levels (odds ratio [OR] = 1.051, 95% fiducial interval [95% CI] = 1.009-1.095, P = 0.02) and oncostatin-M (OSM) levels ( [OR] = 1.041, [95% CI] = 1.001-1.082, P = 0.04) were positively associated with the development of PCOS. Moreover, interleukin-7 (IL-7) levels ([OR] = 0.935, [95% CI] = 0.884-0.989, P = 0.02); interleukin-15 receptor subunit alpha (IL15RA) levels ([OR] = 0.959, [95% CI] = 0.929-0.99, P = 0.01); and C-X-C motif chemokine 11 (CXCL11) levels ([OR] = 0.959, [95% CI] = 0.922-0.996. P = 0.03) were strongly negatively associated with PCOS. However, we did not find any strong positive results in the reverse analysis, suggesting that although inflammatory factors contribute to the pathogenesis of PCOS, PCOS itself does not trigger inflammatory factor production.Our study provides genetic evidence for the connection between systemic inflammatory regulators and PCOS. Treatments targeting specific inflammatory factors may help to mitigate the risk of PCOS. The levels of five of the 91 inflammatory factors included in this study, namely, IL1A and OSM, were associated with PCOS. IL1A and OSM contribute to the progression of PCOS while IL-7, IL15RA, and CXCL11 levels are negatively correlated with the development of PCOS.

Proteome-wide Mendelian randomization and functional studies uncover therapeutic targets for polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is an endocrine syndrome that affects a large portion of women worldwide. This proteogenomic and functional study aimed to uncover candidate therapeutic targets for PCOS. We comprehensively investigated the causal association between circulating proteins and PCOS using two-sample Mendelian randomization analysis. Cis-protein quantitative trait loci were derived from six genome-wide association studies (GWASs) on plasma proteome. Genetic associations with PCOS were obtained from a large-scale GWAS meta-analysis, FinnGen cohort, and UK Biobank. Colocalization analyses were performed to prioritize the causal role of candidate proteins. Protein-protein interaction (PPI) and druggability evaluation assessed the druggability of candidate proteins. We evaluated the enrichment of tier 1 and 2 candidate proteins in individuals with PCOS and a mouse model and explored the potential application of the identified drug target. Genetically predicted levels of 65 proteins exhibited associations with PCOS risk, with 30 proteins showing elevated levels and 35 proteins showing decreased levels linked to higher susceptibility. PPI analyses revealed that FSHB, POSTN, CCN2, and CXCL11 interacted with targets of current PCOS medications. Eighty medications targeting 20 proteins showed their potential for repurposing as therapeutic targets for PCOS. EGLN1 levels were elevated in granulosa cells and the plasma of individuals with PCOS and in the plasma and ovaries of dehydroepiandrosterone (DHEA)-induced PCOS mouse model. As an EGLN1 inhibitor, administration of roxadustat in the PCOS mouse model elucidated the EGLN1-HIF1α-ferroptosis axis in inducing PCOS and validated its therapeutic effect in PCOS. Our study identifies candidate proteins causally associated with PCOS risk and suggests that targeting EGLN1 provides a promising treatment strategy.

Mendelian randomization and multi-omics approach analyses reveal impaired glucose metabolism and oxidative phosphorylation in visceral adipose tissue of women with polycystic ovary syndrome.

What is the significance of visceral adipose tissue (VAT) in the pathogenesis of polycystic ovary syndrome (PCOS) and its impact on the regulation of metabolic disorders in women with PCOS? We revealed a potentially causal relationship between increased genetically predicted VAT and PCOS-related traits, and found that VAT exhibited impaired glucose metabolism and mitochondrial oxidative phosphorylation (OXPHOS) in women with PCOS. PCOS is a common reproductive endocrine disorder accompanied by many metabolic abnormalities. Adipose tissue is a metabolically active endocrine organ that regulates multiple physiological processes, and VAT has a much stronger association with metabolism than subcutaneous adipose tissue does. Mendelian randomization (MR) analysis was used to investigate the potential causal association between genetically predicted VAT and the risk of PCOS. Data for MR analysis were extracted from European population cohorts. VAT samples from sixteen PCOS patients and eight control women who underwent laparoscopic surgery were collected for proteomics and targeted metabolomics analyses. PCOS was diagnosed according to the 2003 Rotterdam Criteria. The control subjects were women who underwent laparoscopic investigation for infertility or benign indications. Proteomics was performed by TMT labeling and liquid chromatography-tandem mass spectrometry analysis, and targeted metabolomics was performed by ultra-performance liquid chromatography-tandem mass spectrometry analysis. The key differentially expressed proteins (DEPs) were validated by immunoblotting. MR analysis revealed a potentially causal relationship between increased genetically predicted VAT and PCOS, as well as related traits, such as polycystic ovaries, total testosterone, bioavailable testosterone, and anti-Müllerian hormone, while a negative relationship was found with sex hormone-binding globulin. Enrichment pathway analysis of DEPs indicated the inhibition of glycolysis and activation of mitochondrial OXPHOS in the VAT of PCOS patients. MR analysis revealed that key DEPs involved in glycolysis and OXPHOS were significantly linked to PCOS and its related traits. Dot blot assay confirmed a significant decrease in glycolysis enzymes PKM2 and HK1, and an increase in mitochondrial Complex I and III subunits, NDUFS3 and UQCR10. Moreover, metabolomics analysis confirmed down-regulated metabolites of energy metabolic pathways, in particular glycolysis. Further analysis of PCOS and control subjects of normal weight revealed that dysregulation of glucose metabolism and OXPHOS in VAT of women with PCOS was independent of obesity. The mass spectrometry proteomics data have been deposited to the iProX database (http://www.iprox.org) with the iProX accession: IPX0005774001. There may be an overlap in some exposure and outcome data, which might affect the results in the MR analysis. The changes in protein expression of key enzymes affect their activities and disrupt the energy metabolic homeostasis in VAT, providing valuable insight for identifying potential intervention targets of PCOS. This work was supported by the National Key Research and Development Project of China (2021YFC2700402), the National Natural Science Foundation of China (82071608, 82271665), the Key Clinical Projects of Peking University Third Hospital (BYSY2022043), and the CAMS Innovation Fund for Medical Sciences (2019-I2M-5-001). All authors report no conflict of interest. N/A.

The Impact of Microparticulate Air Pollution in Polycystic Ovary Syndrome: A Narrative Review

Objective: The aim of this narrative review is to summarize studies examining the relationship between microparticulate air pollution (MAP) and polycystic ovary syndrome (PCOS). Mechanism: PCOS is increasingly regarded as an evolutionary mismatch disorder that manifests in women due to exposure to a range of lifestyle and environmental factors. Although the underlying causes of PCOS remain debated, environmental factors such as endocrine-disrupting chemicals (EDC), may contribute to its pathogenesis due to their well-documented hormonal and metabolic effects. MAP is another significant environmental exposure that has been associated with a variety of chronic diseases, as well as adverse hormonal and metabolic effects, including PCOS. Chronic low-grade inflammation and insulin resistance (IR) are key pathophysiological features of PCOS that have been associated with inhalation and ingestion of MAP. Findings in Brief: Our search identified four studies that systematically examined the relationship between MAP and PCOS. One population-based cohort study showed an increased risk of PCOS with increased exposure to various air pollutants, including MAP. A second population-based study showed a decreased risk of PCOS with increasing levels of exposure, while a longer duration of exposure was associated with an increased risk of PCOS. A third study found that conception rates were lower in women with PCOS exposed to second-hand smoke (SHS) compared to non-exposed women. In contrast, a fourth study reported that exposure to air pollutants was not associated with reduced pregnancy outcomes. These data suggest that both the concentration and duration of exposure to MAP may be important factors, and that reproductive outcomes could be affected by exposure to MAP through second-hand cigarette smoke. Conclusions: Preliminary data suggest that MAP may contribute to an increased risk of PCOS, although the available evidence remains inconsistent. Nevertheless, the current evidence supports advising women to avoid exposure to SHS and MAP whenever possible. This review highlights the need for further research on the effects of MAP in women with PCOS.

Chronotypes in middle-aged women with polycystic ovary syndrome: A population-based study.

Circadian rhythm disruption has been associated with the risk of polycystic ovary syndrome (PCOS), as the evening chronotype (EC) shares several traits with PCOS, including metabolic disorders, cardiovascular diseases, and psychiatric disorders. It has been suggested that the biological clock could be targeted with new, preventive, and therapeutic strategies for PCOS in women with biorhythm disorders. We evaluated inner circadian rhythmicity in middle-aged women with PCOS in a population-based setting, focusing on whether women with PCOS and an EC have a specific subtype in relation to their clinical characteristics. The data derived from the Northern Finland Birth Cohort, a population-based longitudinal birth cohort of 12 058 individuals born in 1966. We compared the circadian phenotype between 314 women with PCOS (according to the Rotterdam criteria) and 1248 women without PCOS at age 46 years using the validated Finnish shortened 6-item Morningness-Eveningness Questionnaire (sMEQ) and the single-item self-assessed morningness-eveningness question. PCOS was not associated with the EC by the sMEQ (p = 0.495) or self-assessment (p = 0.303). The self-assessed morningness-eveningness values differed from the sMEQ chronotype distribution (p < 0.001), nevertheless, the most frequent chronotype was the intermediate chronotype (IC) determined by both chronotyping methods (sMEQ PCOS 47.7% vs. 45.2% non-PCOS; self-assessment PCOS 66.5% vs. 68.4% non-PCOS). The hyperandrogenic PCOS phenotypes A-C did not differ from the non-hyperandrogenic phenotype D as for the chronotype (p = 0.271). The EC was associated in both groups with depressive and anxiety symptoms (PCOS p = 0.012, non-PCOS p < 0.001) and the use of sleep medication (PCOS p = 0.017, non-PCOS p < 0.001). The EC was not over-represented in middle-aged women with PCOS or in the hyperandrogenic PCOS phenotypes A-C in our study. This does not support the need for chronotyping in the comprehensive assessment of women with PCOS. However, as chronotypes tend to change with aging, cross-sectional studies in different age groups are warranted to draw conclusions on the role of chronotypes in PCOS and the associated metabolic risks.

Exploring the causal pathway from gut microbiota to polycystic ovary syndrome: A network Mendelian randomization study.

Polycystic ovary syndrome (PCOS) is a complicated endocrine and metabolic syndrome with unclear pathogenesis. The gut microbiota sheds light on the etiology and pathophysiology of PCOS. We used Mendelian randomization (MR) studies to systematically evaluate the pathological mechanism gut microbiota causally associated with PCOS risk. A network MR analysis was performed to estimate the causal effects of gut microbiota and risk factors on PCOS, as well as the mediation effect of risk factors linking gut microbiota to PCOS. The investigation of side effects for the important gut microbiota was subsequently broadened to include phenotypes by performing Phenowide-MR analysis for a range of diseases. Genus Sellimonas id.14369 were causally associated with reduced PCOS risk (odds ratio [OR] = 0.69, 95% confidence interval [CI]: 0.58-0.84, P = 1.22 × 10-4) after multiple testing correction. And Sellimonas retained consistent causal effect estimates after a series of sensitivity analyses. In addition, we observed an indirect effect of Sellimonas on PCOS through body mass index (BMI) using network MR (b = -0.05, 95% CI: -0.09 to -0.01), with a mediated proportion of 12.82% of the total effect. Further, Phenowide-MR analyses showed that the protective effects of Sellimonas on type 2 diabetes and depression (for type 2 diabetes: OR = 0.95, 95% CI: 0.90-0.99, P = .0366; for depression: OR = 0.99, 95% CI: 0.98-1.00, P = .0210). We summarized that the causal path between gut microbiota and type 2 diabetes are also jointly mediated by BMI. Sellimonas may be a protective factor of PCOS, which can affect the occurrence of PCOS through BMI, supporting future studies on the importance of addressing obesity and metabolic issues in preventing and managing PCOS.

7980 Physical Activity Attenuates the Association of Early Adolescent Adiposity with Later PCOS

Abstract Disclosure: R. Whooten: None. S. Rifas-Shiman: None. W. Perng: None. J. Chavarro: None. E. Oken: None. M. Hivert: None. Purpose: Adiposity is a risk factor for polycystic ovary syndrome (PCOS). Limited knowledge exists regarding modifiable behaviors, such as physical activity, during early-life may mitigate the association of adiposity with PCOS risk. We aimed to assess how moderate-vigorous physical activity (MVPA) may impact the association of adiposity in early adolescence with later report of adolescent PCOS. Methods: Within the Project Viva prospective cohort, we used multivariable logistic regression to assess the association of body mass index z-score (BMIz) at early adolescence (mean age 13.1 years) with mid-late adolescent PCOS (self-reported diagnosis or oligo-anovulation with clinical/biochemical hyperandrogenism at mean age 17.7 years). We stratified our analyses by actigraphy-assessed MVPA during early adolescence (≥30 versus &amp;lt;30 minutes/day). In multivariable models, we adjusted for maternal education and PCOS; and child race and ethnicity, dietary behaviors, actigraphy-assessed sleep duration, and self-reported screentime; and season of actigraphy assessment. Results: Among 341 female adolescents, n=47 (14%) met criteria for PCOS at mid-late adolescence. At early adolescence, mean (SD) BMIz was 0.32 (1.10) units and n=110 (32%) had ≥30 minutes/day MVPA. There was no difference in MVPA ≥30 minutes/day among those with versus without later PCOS (30% vs 33%, p=0.70). In unadjusted analyses, there was an association of early adolescent BMIz with mid-late adolescent PCOS (OR=1.93, 95%CI 1.39, 2.69 per unit increase in BMIz). In stratified analyses, the association of early adolescent adiposity with later PCOS was stronger in those with MVPA &amp;lt;30 minutes/day (OR=2.07, 95%CI 1.37, 3.11) than in those with MVPA ≥30 minutes/day (OR=1.72, 95%CI 0.97, 3.06). These findings persisted after adjusting for all covariates (overall: OR=1.72 95%CI 1.15, 2.56; MVPA &amp;lt;30 min/day: OR=2.01 95%CI 1.17, 3.45; MVPA ≥30 minutes/day: OR=1.36 95%CI 0.64, 2.91), however p-values for interaction terms were non-significant. Conclusion: Our findings suggest that maintaining ≥30 minutes MVPA daily during early adolescence may attenuate the association of adiposity with risk of PCOS by late adolescence. This has implications for the importance of promoting physical activity among at-risk individuals. Presentation: 6/2/2024

Genetic Variations of (SOD2; Rs5746136) and (PON2; Rs705379) are Associated with the Risk Of PCOS and Influence Metabolic Profile Among the Iranian Population

Polycystic ovarian syndrome (PCOS) is one of the most prevalent disorders affecting women's metabolic, psychological, and reproductive features. This study investigated the roles of superoxide dismutase 2 (SOD2; rs5746136) and paraoxonase 2 (PON2; rs705379) gene polymorphisms on the risk of PCOS and oxidative stress and clinical indices in Iranian women. This cross-sectional study included 56 patients (female) with PCOS and 54 healthy women (control group), and single nucleotide polymorphisms (SNPs) of rs5746136 and rs705379 were genotyped. The results showed that there were no detectable variations in frequency between PCOS and control groups in SOD2 genotypes and alleles (p&gt;0.05). Compared with controls, the frequency of rs705379-CC genotype was higher in PCOS individuals [adjusted OR (95%CI) = 2.171 (1.098-4.313), P=0.016], which showed a significant association. While the frequency of the TT genotype was higher in the reference group (OR= 0.464 (0.236-0.97), P=0.015). Patients with the A and C alleles exhibited considerably greater serum levels of luteinizing hormone (LH) and LH/FSH (follicle-stimulating hormone) than the control group. Our results revealed that the PON1 gene (C&gt;T) polymorphism is related to the risk of PCOS. However, the SOD2 gene (G&gt;A) polymorphism in our study population did not show any relation to PCOS. Importantly, oxidative stress parameters showed a significant relationship with PON1 rs705379-genotype.

Causal relationship between fertility nutrients supplementation and PCOS risk: a Mendelian randomization study.

Polycystic ovary syndrome (PCOS), a prevalent endocrine disorder in women of reproductive age, is mainly ameliorated through drugs or lifestyle changes, with limited treatment options. To date, numerous researchers have found that fertility nutrient supplements may benefit female reproductive health, but their direct impact on polycystic ovary syndrome risk remains unclear. Our research employs Mendelian Randomization to assess how fertility nutrients affect PCOS risk. Initially, we reviewed 49 nutrients and focused on 10: omega-3 fatty acids, calcium, dehydroepiandrosterone, vitamin D, betaine, D-Inositol, berberine, curcumin, epigallocatechin gallate, and metformin. Using methodologies of Inverse Variance Weighting and Mendelian Randomization-Egger regression, we examined their potential causal relationships with PCOS risk. Our findings indicate omega-3 fatty acids reduced PCOS risk (OR=0.73, 95% CI: 0.57-0.94, P=0.016), whereas betaine increased it (OR=2.60, 95% CI: 1.09-6.17, P=0.031). No definitive causal relations were observed for calcium, dehydroepiandrosterone, vitamin D, D-Inositol, and metformin (P>0.05). Drug target Mendelian Randomization analysis suggested that increased expression of the berberine target gene BIRC5 in various tissues may raise PCOS risk (OR: 3.00-4.88; P: 0.014-0.018), while elevated expressions of curcumin target gene CBR1 in Stomach and epigallocatechin gallate target gene AHR in Adrenal Gland were associated with reduced PCOS risk (OR=0.48, P=0.048; OR=0.02, P=0.018, respectively). Our research reveals that specific fertility nutrients supplementation, such as omega-3 fatty acids, berberine, and curcumin, may reduce the risk of PCOS by improving metabolic and reproductive abnormalities associated with it.

Elucidating the molecular interactions and immune modulation of bisphenols exposure in the pathogenesis of polycystic ovary syndrome

Bisphenols (BPs) are known endocrine disruptors potentially contributing to the pathogenesis of Polycystic Ovary Syndrome (PCOS). This study aims to elucidate the molecular interactions between BPs and PCOS-related genes and their combined effects on PCOS development. We identified common genes associated with BPs and PCOS using the CTD. Differential expression analysis was performed on three GEO datasets, leading to the identification of differentially expressed genes (DEGs). Protein-Protein Interaction (PPI) network construction, enrichment analysis, single-gene Gene Set Enrichment Analysis (GSEA), and immune cell infiltration analysis were carried out. A nomogram was developed for PCOS risk prediction, and molecular docking studies were performed using AutoDock Vina, with interaction visualizations via PyMOL. We identified 139 common genes between BPs exposure and PCOS, enrichment analysis highlighted pathways related to hormone metabolism, ovarian steroidogenesis, and p53 signaling. Four hub DEGs (PBK, CCNE2, LPCAT2, S100P) were identified, and a nomogram incorporating these genes demonstrated excellent predictive accuracy. GSEA revealed roles in cell adhesion, immune response, and metabolism. ssGSEA analysis showed significant differences in immune cell infiltration between PCOS and control groups, with notable correlations between hub DEGs and immune cells. Molecular docking indicated strong binding affinities between the hub DEGs and BPAF, suggesting potential disruptions induced by BPs. BPs exposure is associated with significant molecular and immunological changes in PCOS, impacting genes involved in hormone regulation, immune response, and metabolic pathways. The strong binding affinities between BPs and key PCOS-related genes reveal their potential role in exacerbating PCOS, providing insights for targeted therapeutic strategies.

Unraveling the Mysteries of PCOS: A Comprehensive Investigation into Causes, Mechanisms, and Molecular Docking Analysis with Dolichos biflorus Linn.

Abstract: Polycystic ovary syndrome (PCOS) presents as a complex endocrine and metabolic disorder characterized by anovulation, infertility, obesity, insulin resistance, and polycystic ovaries. Various factors contribute to PCOS risk, including lifestyle choices, diet, environmental pollutants, genetics, gut dysbiosis, neuroendocrine changes, and obesity. These factors can impact hyperinsulinemia, oxidative stress, hyperandrogenism, decreased folliculogenesis, and irregular menstrual cycles, ultimately contributing to metabolic syndrome. Conventional treatments for PCOS often carry significant side effects, prompting exploration into Ayurvedic alternatives. This review concentrates on molecular docking studies of phytochemicals sourced from Dolichos Biflorus Linn. against key proteins implicated in PCOS pathogenesis. Identification, modeling, and evaluation of target proteins were conducted, followed by the assessment of their interactions with selected phytochemicals and additional ADMET analysis. Molecular docking studies utilizing Auto Dock Vina software were then performed to forecast the binding affinities of these phytochemicals to the active sites of the specified targets.

From proteome to pathogenesis: investigating polycystic ovary syndrome with Mendelian randomization analysis.

Polycystic ovary syndrome (PCOS) is defined by oligo/anovulation, hyperandrogenism, and polycystic ovaries with uncertain pathogenesis. The proteome represents a substantial source of therapeutic targets, and their coding genes may elucidate the mechanisms underlying PCOS. However, reports on the profiles of the human plasma protein-coding genes and PCOS are limited. Here, we aimed to investigate novel biomarkers or drug targets for PCOS by integrating genetics and the human plasma proteome. Our study acquired the protein quantitative trait loci from DECODE Genetics, offering 4,907 proteins in 35,559 individuals while obtaining PCOS summary statistics by accessing the FinnGen biobank (1,639 cases and 218,970 controls) and the genome-wide association study catalog (797 cases and 140,558 controls). Herein, we sequentially used two-sample Mendelian randomization (MR) analyses and colocalization to verify the causal link between candidate proteins, their coding genes, and PCOS. Further PCOS data download was conducted by accessing the Gene Expression Omnibus and Zenodo platforms. Gene expression level analysis, pathway enrichment analysis, immune cell infiltration, and transcription factor prediction were performed, aiming at detecting specific cell types with enriched expression and exploring potential optimized treatments for PCOS. MR analysis revealed 243 protein-coding genes with a causal relationship to PCOS risk, of which 12 were prioritized with the most significant evidence. Through colocalization analysis, three key genes, CUB domain-containing protein 1 (CDCP1), glutaredoxin 2 (GLRX2), and kirre-like nephrin family adhesion molecule 2 (KIRREL2), were identified. Subsequently, the three genes were strongly related to immune function and metabolism in terms of biological significance. In single-cell analysis, the expression levels of genes in ovarian theca cells were explored. Overall, three protein-coding genes (CDCP1, GLRX2, and KIRREL2) may be related to a higher PCOS risk, suggesting that they may be entry points for exploration of PCOS pathogenesis and treatment, warranting further clinical investigations.

Molecular study of CYP21 gene polymorphism rs13405728 and CYP11A1 gene polymorphism rs4077582 in polycystic ovarian syndrome patients

BackgroundPCOS is a serious endocrine-metabolic condition characterized by hyperandrogenemia, anovulation, or oligo-ovulation, and links to obesity, insulin resistance, and an elevated risk of type 2 diabetes mellitus. The pathophysiology of PCOS is thought to involve both environmental and genetic factors. PCOS etiology has been linked to genetic factors, with the CYP21 and CYP11A1 genes identified as possible candidate genes. Previous research has linked the rs13405728 polymorphism in the CYP21 gene and the rs4077582 polymorphism in the CYP11A1 gene to PCOS. However, more research is needed to confirm these connections in specific populations. The purpose of this study was to look at the role of single gene polymorphisms in PCOS, specifically the rs13405728 polymorphism in the CYP21 (LHCGR) gene and the rs4077582 polymorphism in the CYP11A1 gene. Blood was drawn from 150 PCOS patients and 150 age- and gender-matched healthy people. The phenol–chloroform procedure was used to extract DNA, and gel electrophoresis was used to quantify it. To analyze polymorphisms, researchers used polymerase chain reaction (PCR) with the allele-specific amplification refractory mutation system (ARMS-PCR) to amplify specific areas of DNA. ARMS-PCR was used to detect mutations in the CYP21 and CYP11A1 genes, followed by sequencing to examine the rs13405728 polymorphism and rs4077582 polymorphism, respectively, in 150 PCOS patients and 150 control people. ARMS-PCR polymorphism study of the CYP21 (LHCGR) and CYP11A1 genes indicated significant correlations.ResultsFor the CYP21 gene, heterozygous (CT) carriers of the rs13405728 polymorphism had a fourfold greater incidence of PCOS (OR 4.10; CI 2.47–6.80; p = 0.0001), whereas homozygous mutant (TT) carriers had a significant connection with PCOS (OR 0.27; CI 0.16–0.45; p = 0.0001). These data imply that the CYP21 (LHCGR) gene polymorphism rs13405728 has a substantial impact on the development of polycystic ovarian syndrome. The data for the CYP11A1 gene show the SNP (rs4077582) heterozygous (CT) was associated with PCOS (OR 1.72; 95% CI 1.02–2.88; p = 0.0392). The identical SNP heterozygous (CT) raised the incidence of PCOS by up to onefold. The homozygous mutant SNP (TT) had no connection with illness onset (OR 1.377; 95% CI 0.85–2.2; p = 0.1855), while the mutant (TT) of the SNP nearly doubled the incidence of polycystic ovarian syndrome. The combined model of the same SNP (CT + TT) revealed a significant correlation with PCOS (OR 2.1905; 95% CI 1.355–3.53; p = 0.0014). The combination model (CT + TT) of the same SNP more than doubled the risk of polycystic ovarian syndrome. All the risk factors investigated had a substantial connection with PCOS.ConclusionIn conclusion, this study supports the role of the CYP21 (LHCGR) and CYP11A1 gene polymorphism in PCOS. More studies are needed to investigate the functional significance of this polymorphism as well as its possible clinical impact on the diagnosis and treatment of PCOS.

Association of candidate gene (INSR & THADA) polymorphism with polycystic ovary syndrome: meta-analysis and statistical power analysis.

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that impacts women before reaching menopause. In addition to notable features (irregular ovulation, elevated androgen levels, and the existence of numerous ovarian cysts), individuals with PCOS frequently encounter diverse metabolic, cardiovascular, and psychological conditions. The onset of PCOS is influenced by a combination of factors, and various genetic variations are believed to play a significant role in its progression. The objective of the current study was to explore the link between genetic variations in the candidate genes thyroid-adenoma-associated (THADA) gene and insulin receptor (INSR) and susceptibility to developing PCOS. We conducted an extensive search across various databases, including Google Scholar, PubMed, Science Direct, Scopus, and EMBASE, to compile relevant case-control studies and literature reviews for subsequent statistical analysis. In the present study, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was followed, a guideline for Systematic Reviews and Meta-Analysis. While a previous meta-analysis explored the correlation between INSR rs1799817 and THADA rs13429458 and their association with susceptibility to PCOS, our current study did not integrate any findings from these prior investigations. Our research encompassed articles published between 2017 and 2023, and we employed MetaGenyo software to assess the collected data. Statistical power analysis was performed using G*Power 3.1 software. Odds ratios and their corresponding 95% confidence intervals were calculated for each genetic model. Fifteen studies that met the criteria were analyzed. Out of these, ten studies, involving 1,189 cases and 1,005 controls, examined the INSR rs1799817 gene polymorphism, while five studies, including 783 cases and 553 controls, investigated the THADA rs13429458 gene polymorphism. The meta-analysis results indicated that there was no statistically significant association between the INSR rs1799817 gene polymorphism and the risk of PCOS (p>0.05). In contrast, the THADA rs13429458 gene polymorphism showed a significant association with PCOS risk under the over-dominant model (p<0.05). The present meta-analysis demonstrated a notable association between the THADA rs13429458 gene polymorphism and the likelihood of developing PCOS. Further rigorous studies with expanded sample sizes and diverse ethnic representation will be important to comprehensively evaluate and validate these findings.

Exploring Genetic Interactions in Colombian Women with Polycystic Ovarian Syndrome: A Study on SNP-SNP Associations.

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with high prevalence in women around the world. The identification of single-nucleotide polymorphisms (SNPs) through genome-wide association studies has classified it as a polygenic disease. Most studies have independently evaluated the contribution of each SNP to the risk of PCOS. Few studies have assessed the effect of epistasis among the identified SNPs. Therefore, this exploratory study aimed to evaluate the interaction of 27 SNPs identified as risk candidates and their contribution to the pathogenesis of PCOS. The study population included 49 control women and 49 women with PCOS with a normal BMI. Genotyping was carried out through the MassARRAY iPLEX single-nucleotide polymorphism typing platform. Using the multifactor dimensionality reduction (MDR) method, the interaction between SNPs was evaluated. The analysis showed that the best interaction model (p < 0.0001) was composed of three loci (rs11692782-FSHR, rs2268361-FSHR, and rs4784165-TOX3). Furthermore, a tendency towards synergy was evident between rs2268361 and the SNPs rs7371084-rs11692782-rs4784165, as well as a redundancy in rs7371084-rs11692782-rs4784165. This pilot study suggests that epistasis may influence PCOS pathophysiology. Large-scale analysis is needed to deepen our understanding of its impact on this complex syndrome affecting thousands of women.

Polycystic Ovary Syndrome and the Internet of Things: A Scoping Review.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder impacting women's health and quality of life. This scoping review explores the use of the Internet of Things (IoT) in PCOS management. Results were grouped into six domains of the IoT: mobile apps, social media, wearables, machine learning, websites, and phone-based. A further domain was created to capture participants' perspectives on using the IoT in PCOS management. Mobile apps appear to be useful for menstrual cycle tracking, symptom recording, and education. Despite concerns regarding the quality and reliability of social media content, these platforms may play an important role in disseminating PCOS-related information. Wearables facilitate detailed symptom monitoring and improve communication with healthcare providers. Machine learning algorithms show promising results in PCOS diagnosis accuracy, risk prediction, and app development. Although abundant, PCOS-related content on websites may lack quality and cultural considerations. While patients express concerns about online misinformation, they consider online forums valuable for peer connection. Using text messages and phone calls to provide feedback and support to PCOS patients may help them improve lifestyle behaviors and self-management skills. Advancing evidence-based, culturally sensitive, and accessible IoT solutions can enhance their potential to transform PCOS care, address misinformation, and empower women to better manage their symptoms.

A metabolome-wide Mendelian randomization study prioritizes causal circulating metabolites for reproductive disorders including primary ovarian insufficiency, polycystic ovary syndrome, and abnormal spermatozoa

BackgroundAccumulating studies have highlighted the significant role of circulating metabolomics in the etiology of reproductive system disorders. However, the causal effects between genetically determined metabolites (GDMs) and reproductive diseases, including primary ovarian insufficiency (POI), polycystic ovary syndrome (PCOS), and abnormal spermatozoa (AS), still await thorough clarification.MethodsWith the currently most comprehensive genome-wide association studies (GWAS) data of metabolomics, systematic two-sample Mendelian randomization (MR) analyses were conducted to disclose causal associations between 1,091 blood metabolites and 309 metabolite ratios with reproductive disorders. The inverse-variance weighted (IVW) method served as the primary analysis approach, and multiple effective MR methods were employed as complementary analyses including MR-Egger, weighted median, constrained maximum likelihood (cML-MA), contamination mixture method, robust adjusted profile score (MR-RAPS), and debiased inverse-variance weighted method. Heterogeneity and pleiotropy were assessed via MR-Egger intercept and Cochran’s Q statistical analysis. Outliers were detected by Radial MR and MR-PRESSO methods. External replication and metabolic pathway analysis were also conducted.ResultsPotential causal associations of 63 GDMs with POI were unearthed, and five metabolites with strong causal links to POI were emphasized. Two metabolic pathways related to the pathogenesis of POI were pinpointed. Suggestive causal effects of 70 GDMs on PCOS were detected, among which 7 metabolites stood out for strong causality with elevated PCOS risk. Four metabolic pathways associated with PCOS mechanisms were recognized. For AS, 64 GDMs as potential predictive biomarkers were identified, particularly highlighting two metabolites for their strong causal connections with AS. Three pathways underneath the AS mechanism were identified. Multiple assessments were conducted to further confirm the reliability and robustness of our causal inferences.ConclusionBy extensively assessing the causal implications of circulating GDMs on reproductive system disorders, our study underscores the intricate and pivotal role of metabolomics in reproductive ill-health, laying a theoretical foundation for clinical strategies from metabolic insights.

The Association of Vitamin D Receptor Gene Polymorphism with Polycystic Ovary Syndrome in a Southeast Iranian Population

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder among women of reproductive age, characterized by hyperandrogenism, amenorrhea, and polycystic ovaries. Metabolic disorders, including insulin resistance (IR), are common comorbidities of PCOS, with vitamin D receptors playing a crucial role. Objectives: We investigated whether the rs2228570T &gt; C variant of the vitamin D receptor (VDR) gene is associated with the risk of PCOS. Methods: In the current study, 112 women with PCOS and 150 healthy women participated. Genomic DNA was extracted using the standard salting-out method. Genotyping of rs2228570T &gt; C was conducted via amplification-refractory mutation system polymerase chain reaction. Additionally, VD3 levels were measured using the ELISA system. Statistical analysis of genotyping data was performed using the SPSS V.22 package. Results: The statistical analysis showed that the T-allele of rs2228570C/T significantly decreased the risk of PCOS. Moreover, the T-allele in the codominant model significantly eliminated the risk of PCOS in our population. Our results also showed a statistically significant difference in VD3 levels between the CC and TT genotypes. Conclusions: Based on our result, rs228570C/T had a protective role for PCOS risk in our population.