Deciphering the molecular connections between polycystic ovarian syndrome and autism spectrum disorder using bioinformatic analysis.

There is emerging evidence demonstrating an association between maternal polycystic ovary syndrome (PCOS) and autism spectrum disorder (ASD) in children, however, the cumulative effect of maternal PCOS on the development of ASD or other neuropsychiatry disorders (NPD) in children and separately for males and females has not been examined. We sought to systematically evaluate the influence of maternal PCOS on a wide range of NPD including ASD, attention deficit hyperactivity disorder (ADHD), chronic tic disorder (CDT), other behavior disorders, anxiety, depression, bipolar disorder, schizophrenia in children as well as in women of reproductive age only. We queried electronic databases including PubMed, EMBASE, and Google Scholar, until March 2021. We used DerSimonian and Laird (D-L) random effects method to compute pooled effect size in terms of odds ratio (OR). Nineteen studies (1667851 mothers, 2260622 children) were included in this study. Mothers with PCOS had an increased odds of children diagnosed with ASD (OR = 1.40, p < 0.001), ADHD (OR = 1.42, p < 0.001), CTD (OR = 1.44, p = 0.001), anxiety (OR = 1.33, p < 0.001), as well as other behavioral symptoms (OR = 1.45, p < 0.001) in the adjusted analysis. The association between maternal PCOS and ASD (OR: 1.43 vs. 1.66), ADHD (OR: 1.39 vs. 1.54), and CTD (OR: 1.42 vs. 1.51) was found to be significantly consistent between males and females, respectively. Our data do not suggest increased fetal testosterone exposure is associated with increased autistic traits in children. However, PCOS was significantly associated with increased odds of a wide range of NPD in women themselves. Maternal PCOS is a risk factor for various NPD with a similar extent in their children regardless of their underlying comorbidities. Managing PCOS is essential for women’s health as well as for their children’s health. More research is needed to determine the mechanisms and links between maternal PCOS and NPD in children.

Journal Digest

A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome

Integrative bioinformatics and transcriptomic analysis identifies biomarkers in Polycystic Ovary Syndrome through machine learning approach.

Study question What is the underlying mechanism contributing to the transgenerational defects of oocytes and embryos of polycystic ovary syndrome (PCOS)? Summary answer The transgenerational inheritance of abnormal chromatin accessibility in the PCOS oocytes is responsible for the defect of oocytes and embryos in transgeneration. What is known already Studies have provided evidence of compromised oocyte quality and related adverse impacts. Observed PCOS animal-model oocyte defects include meiotic abnormalities, mitochondrial dysfunction, and increased oxidative stress. Elevated androgen levels are associated with reduced fertilization rates and lower cleavage rates during in vitro fertilization (IVF) treatment. PCOS could be transgenerationally transmitted, and unique altered gene expression has been observed in metaphase II (MII) oocytes from all offspring in PCOS mice. Study design, size, duration We profiled the transcriptome and chromatin accessibility of oocytes and preimplantation embryos in F0-F2 offspring of PCOS mice, to explored whether the inheritance of chromatin accessibility defects in PCOS oocytes was responsible for the abnormalities of oocytes and embryos in PCOS offspring. Besides, oocytes from 13 healthy women and 8 women with PCOS, 24 blood samples from 24 women with/without PCOS were analyzed to validate the molecular mechanisms of PCOS inheritance. Duration: 2019.5∼2022.12. Participants/materials, setting, methods PCOS mice models were established by means of DHEA-exposure. Smart-seq2 and DNase-seq were utilized to investigate the transcriptome and chromatin accessibility of oocytes and preimplantation embryos in F0-F2 offspring of PCOS mice. Bioinformatic analysis was applied to explore the differential gene expression and chromatin accessibility of oocytes and embryos in PCOS mice and offspring comparing to controls. Common gene signatures in the tissues of PCOS women and PCOS daughters are analyzed compared to control samples. Main results and the role of chance In PCOS mice, we observed transcriptional alteration in oocytes and 2-cell embryos compared to normal mice. There are 4229 and 1197 differentially expressed genes (DEGs) in PCOS oocytes and 2-cell embryos. The DEGs includes both maternal factors and zygotic genome activation (ZGA) genes. Interestingly, in PCOS 2-cell embryos, we observed hundreds of pre-activated genes which are silence in normal 2-cell embryo but expressed in PCOS 2-cell embryos. Notably, many DEGs in the oocytes of PCOS mice were also differentially expressed in the oocytes of F2 PCOS mice compared to control mice, supporting the transgenerational inheritance of transcriptional alteration in PCOS oocytes. Mechanismly, the changes of chromatin accessibility were associated with the DEGs in PCOS oocytes and embryos. In particular, chromatin accessibility of the pre-activated gene promoters is elevated in PCOS oocytes compared to that in normal oocytes. Furthermore, many of the abnormal chromatin accessibility signals detected in F0 PCOS oocytes were also observed in F2 PCOS oocytes. Finally, our data showed that some DEGs in the oocytes of PCOS mice were also differentially expressed in human PCOS oocytes compared to the control oocytes. Common genes identified in PCOS offspring may be used as potential predictors of PCOS phenotype. Limitations, reasons for caution Which factors contribute to the abnormalities of chromatin accessibility in PCOS oocytes are still unknown. Wider implications of the findings The candidate genes may be used as potential predictors of PCOS phenotype and provide the clues for PCOS offspring . Trial registration number not applicable

Background:The aim of this study was to find underlying genes and their interaction mechanism crucial to the polycystic ovarian syndrome (PCOS) by analyzing differentially expressed genes (DEGs) between PCOS and non-PCOS subjects.Methods:Gene expression data of PCOS and non-PCOS subjects were collected from gene expression omnibus (GEO) database. GEO2R were used to calculating P value and logFC. The screening threshold of DEGs was P < .05 and | FC | ≥ 1.2. GO annotation and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis was performed by using DAVID (2021 Update). The protein-protein interaction (PPI) network of DEGs was constructed by using the STRING database, and the hub genes were recognized through Hubba plugin of Cytoscape software.Results:PCOS and non-PCOS subjects shared a total of 174 DGEs, including 14 upregulated and 160 downregulated genes. The GO biological processes enriched by DEGs mainly involved actin cytoskeleton organization, positive regulation of NF-κB signaling pathway, and positive regulation of canonical Wnt signaling pathway. The DEGs were significantly enriched in cytoplasm, nucleus and cytosol. Their molecular functions mainly focused on protein binding, calmodulin binding and glycerol-3-phosphate dehydrogenase activity. The PI3K/Akt signaling pathway and glycosaminoglycan biosynthesis were highlighted as critical pathways enriched by DEGs. 10 hub genes were screened from the constructed PPI network, of which EGF, FN1 and TLR4 were mainly enriched in the PI3K/Akt signaling pathway.Conclusion:In this study, a total of 174 DEGs and 10 hub genes were identified as new candidate targets for insulin resistance (IR) in PCOS individuals, which may provide a new direction for developing novel treatment strategies for PCOS.

Is maternal polycystic ovary syndrome (PCOS) associated with increased risks for a broad spectrum of psychiatric and mild neurodevelopmental disorders in offspring? Maternal PCOS and/or anovulatory infertility is independently, and jointly with maternal obesity, perinatal problems, cesarean delivery and gestational diabetes, associated with increased risks in offspring for almost all groups of psychiatric and mild neurodevelopmental disorders with onset in childhood or adolescence. Maternal PCOS was previously associated with autism spectrum disorder, attention-deficit/hyperactivity disorders and possibly developmental delay in offspring. Few studies have investigated the association between maternal PCOS and other psychiatric and neurodevelopmental disorders in offspring. This was a population-based cohort study in Finland including all live births between 1996 and 2014 (n = 1 105 997). After excluding births to mothers with symptoms similar to PCOS, a total of 1 097 753 births by 590 939 mothers remained. Children were followed up until 31 December 2018, i.e. up to the age of 22 years. National registries were used to link data of the included births and their mothers. Data from 24 682 (2.2%) children born to mothers with PCOS were compared with 1 073 071 (97.8%) children born to mothers without PCOS. Cox proportional hazards modeling was used to evaluate the hazard ratio (HR) and 95% CI for the risk of neuropsychiatric disorders in relation to maternal PCOS. Stratified analyses were performed to test the independent role of PCOS and the joint effects of PCOS with maternal obesity, perinatal problems, cesarean delivery, gestational diabetes and use of fertility treatment. The analysis was adjusted for maternal age, country of birth, marriage status at birth, smoking, parity, psychiatric disorders, prescription of psychotropic N05/N06 during pregnancy and systemic inflammatory diseases when applicable. A total of 105 409 (9.8%) children were diagnosed with a neurodevelopmental or psychiatric disorder. Firstly, maternal PCOS was associated with any psychiatric diagnosis (HR 1.32; 95% CI 1.27-1.38) in offspring. Particularly, the risk was increased for sleeping disorders (HR 1.46; 95% CI 1.27-1.67), attention-deficit/hyperactivity disorders and conduct disorders (HR 1.42; 95% CI 1.33-1.52), tic disorders (HR 1.42; 95% CI 1.21-1.68), intellectual disabilities (HR 1.41; 95% CI 1.24-1.60), autism spectrum disorder(HR 1.40; 95% CI 1.26-1.57), specific developmental disorders (HR 1.37; 95% CI 1.30-1.43), eating disorders (HR 1.36; 95% CI 1.15-1.61), anxiety disorders (HR 1.33; 95% CI 1.26-1.41), mood disorders (HR 1.27; 95% CI 1.18-1.35) and other behavioral and emotional disorders (ICD-10 F98, HR 1.49; 95% CI 1.39-1.59). In short, there was no significant difference between sexes. The results were robust when restricting the analyses to the first-born children or births to mothers without psychiatric diagnosis or purchase of psychotropic medication. Secondly, stratified analysis according to maternal BMI showed that the risk of any neuropsychiatric disorder was increased in offspring to normal-weight mothers with PCOS (HR 1.20; 95% CI 1.09-1.32), and markedly higher in those to severely obese mothers with PCOS (HR 2.11; 95% CI 1.76-2.53) compared to offspring to normal-weight mothers without PCOS. When excluding perinatal problems, mothers with PCOS were still associated with increased risks of any neuropsychiatric disorders in offspring (HR 1.28; 95% CI 1.22-1.34) compared to mothers without PCOS. However, an additional increase was observed for PCOS in combination with perinatal problems (HR 1.99; 95% CI 1.84-2.16). Likewise, excluding cases with maternal gestational diabetes (HR 1.30; 95% CI 1.25-1.36), cesarean delivery (HR 1.29; 95% CI 1.23-1.35) or fertility treatment (HR 1.31; 95% CI 1.25-1.36) did not eliminate the associations. The register-based prevalence of PCOS was lower than previously reported, suggesting that this study may capture the most severe cases. To combine anovulatory infertility with PCOS diagnosis as PCOS exposure might introduce diagnostic bias. It was not feasible to distinguish between subtypes of PCOS. Furthermore, familial factors might confound the association between maternal PCOS and neuropsychiatric disorders in offspring. Maternal BMI was available for birth cohort 2004-2014 only and there was no information on gestational weight gain. This study provides further evidence that maternal PCOS and/or anovulatory infertility, independently and jointly with maternal obesity, perinatal problems, gestational diabetes and cesarean delivery, implies a broad range of adverse effects on offspring neurodevelopment. These findings may potentially help in counseling and managing pregnancies. This study was supported by the joint research funding of Shandong University and Karolinska Institute (SDU-KI-2019-08 to X.C and C.L.), THL Finnish Institute for Health and Welfare: Drug and pregnancy project [M.G.], the Swedish Research Council [2014-10171 to C.L.], the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and Karolinska Institute Stockholm County Council [SLL20170292 to C.L.], the Swedish Brain Foundation [FO2018-0141 and FO2019-0201 to C.L.]. X.C. was supported by the China Scholarship Council during her training in Karolinska Institute. L.K. was supported by the China Scholarship Council for his PhD study in Karolinska Institute. The authors have no competing interests to disclose. N/A.

Background: Polycystic ovary syndrome (PCOS) is the most common metabolic and endocrinopathies disorder in women of reproductive age and non-alcoholic fatty liver (NAFLD) is one of the most common liver diseases worldwide. Previous research has indicated potential associations between PCOS and NAFLD, but the underlying pathophysiology is still not clear. The present study aims to identify the differentially expressed genes (DEGs) between PCOS and NAFLD through the bioinformatics method, and explore the associated molecular mechanisms. Methods: The microarray datasets GSE34526 and GSE63067 were downloaded from Gene Expression Omnibus (GEO) database and analyzed to obtain the DEGs between PCOS and NAFLD with the GEO2R online tool. Next, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for the DEGs were performed. Then, the protein-protein interaction (PPI) network was constructed and the hub genes were identified using the STRING database and Cytoscape software. Finally, NetworkAnalyst was used to construct the network between the targeted microRNAs (miRNAs) and the hub genes. Results: A total of 52 genes were identified as DEGs in the above two datasets. GO and KEGG enrichment analysis indicated that DEGs are mostly enriched in immunity and inflammation related pathways. In addition, nine hub genes, including TREM1, S100A9, FPR1, NCF2, FCER1G, CCR1, S100A12, MMP9, and IL1RN were selected from the PPI network by using the cytoHubba and MCODE plug-in. Then, four miRNAs, including miR-20a-5p, miR-129-2-3p, miR-124-3p, and miR-101-3p, were predicted as possibly the key miRNAs through the miRNA-gene network construction. Conclusion: In summary, we firstly constructed a miRNA-gene regulatory network depicting interactions between the predicted miRNA and the hub genes in NAFLD and PCOS, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for PCOS and NAFLD.

There is evidence showing a positive correlation between prenatal androgens and their effect on the development of central nervous system and the autistic spectrum disorder (ASD) phenotype in offspring of mothers with polycystic ovary syndrome (PCOS). We applied a systematic review to investigate whether women with PCOS have increased odds of having a child with ASD, while, secondarily, if these women themselves are at high risk of having the disease. Major databases from inception until 14th October 2018 were searched. The primary outcome measure was the odds of an ASD diagnosis in children of mothers with diagnosed PCOS, while the secondary outcome was the odds of ASD diagnosis in women with PCOS. Scheduled subgroup analyses were according to the time of birth and maternal age. We assessed the odds ratio (OR), using a random-effects model; heterogeneity was assessed by I2 and τ2 statistics. The quality of the evidence was evaluated using the Newcastle-Ottawa Scale. Ten studies were eligible for inclusion, including a total of 33,887 ASD children and 321,661 non-ASD children. Diagnosed PCOS was associated with a 1.66 times increase in the odds of ASD in the offspring [95% CI: 1.51, 1.83, p = 1.99 × 10-25, 7 studies, I2 = 0%, τ2 = 0]. Women with PCOS were 1.78 times more likely to be diagnosed with ASD (95% CI: 1.10, 2.87, p = 0.0179, 5 studies, I2 = 85.4%, τ2 = 0.2432). Additional analyses did not change the initial result. The overall quality of the evidence was high. The pooled effects size displayed low heterogeneity (I2 = 0%) for the primary outcome. While the heterogeneity in the secondary outcome appears to attenuate when only high quality studies are synthesized, still the result exhibits significant heterogeneity. Τhe available data allowed a subgroup analysis only for classification system for PCOS diagnosis and showed a significant increase of ASD diagnosis in the offspring of women with Read Code and ICD diagnosed PCOS. In conclusion, the available evidence suggests that women with PCOS have increased odds of having a child with ASD, an effect size estimate based on a large number of patients from studies of good quality. Regarding the evidence on the prevalence of ASD in PCOS women, results suggest that women with PCOS are more likely to be diagnosed with ASD.

BackgroundChanges in the oxidative stress and lipid metabolism (OSLM) pathways play important roles in polycystic ovarian syndrome (PCOS) pathogenesis and development. Consequently, a systematic analysis of genes related to OSLM was conducted to identify molecular clusters and explore new biomarkers that are helpful for the diagnostic of PCOS.MethodsGene expression and clinical data from 22 PCOS women and 14 normal women were obtained from the GEO database (GSE34526, GSE95728, and GSE106724). Consensus clustering identified OSLM-related molecular clusters, and WGCNA revealed co-expression patterns. The immune microenvironment was quantitatively assessed utilizing the CIBERSORT algorithm. Multiple machine learning models and connectivity map analyses were subsequently applied to explore potential biomarkers for PCOS, and nomograms were employed to develop a predictive multigene model of PCOS. Finally, the OSLM status of PCOS and the hub genes expression profiles were preliminarily verified using TUNEL, qRT‒PCR, western blot, and IHC assays in a PCOS mouse model.Results19 differential expression genes (DEGs) related to OSLM were identified. Based on 19 DEGs that were strongly influenced by OSLM, PCOS patients were stratified into two distinct clusters, designated Cluster 1 and Cluster 2. Distinct differences in the immune cell proportions existed in normal and two PCOS clusters. The random forest showed the best results, with the least cross-entropy and the utmost AUC (cross-entropy: 0.111 AUC: 0.960). Among the 19 OSLM-related genes, CXCR1, ACP5, CEACAM3, S1PR4, and TCF7 were identified by a Bayesian network and had a good fit with PCOS disease risk by the nomogram (AUC: 0.990 CI: 0.968–1.000). TUNEL assays revealed more severe DNA damage within the ovarian granule cells of PCOS mice than in those of normal mice (P < 0.001). The RNA and protein expression levels of the five hub genes were significantly elevated in PCOS mice, which was consistent with the results of the bioinformatics analyses.ConclusionA novel predictive model was constructed for PCOS patients and five hub genes were identified as potential biomarkers to offer novel insights into clinical diagnostic strategies for PCOS.

PCOS is a common endocrine disorder in women of reproductive age, with granulosa cells playing a key role in its development. This study aims to identify shared differentially expressed genes (DEG) in granulosa cells and blood from PCOS patients, offering potential biomarkers and therapeutic targets. Transcriptomic data were obtained from the Gene Expression Omnibus (GEO) database: GSE95728 (granulosa cells; 7 PCOS, 7 controls) and two blood-based datasets, GSE85932 and GSE54248 (12 PCOS, 12 controls). In silico tools were employed to identify DEG, hub genes, and protein-protein interactions and to explore predicted drug targets. DEG analysis revealed that Vanin-2 (VNN2) and Interleukin-1 receptor type 2 (IL1R2) were consistently dysregulated in PCOS patients. Dysferlin (DYSF), Carbonic Anhydrase 4 (CA4), and Solute Carrier Family 2 Member 14 (SLC2A14) were differentially expressed between the blood datasets, while Aquaporin 9 (AQP9), C-X-C Motif Chemokine Receptor 1 (CXCR1), and Annexin A3 (ANXA3) were dysregulated in GSE95728 (granulosa cells) and GSE54248 (blood). Functional enrichment highlighted immune and metabolic pathways. Protein-protein interaction analysis identified AQP9 as a hub gene. Drug prediction analysis suggested that IL1R2 could be targeted by anakinra, while VNN2 was predicted to interact with pantothenic acid. The dysregulation of VNN2 and IL1R2 across tissue types suggests their involvement in immune-inflammatory processes in PCOS. The expression of AQP9 and other metabolism-related genes indicates possible immune-metabolic crosstalk, aligning with known PCOS pathophysiology. VNN2 and IL1R2 show potential as biomarkers or therapeutic targets in PCOS. Further validation is needed to confirm their clinical significance and roles.

Maternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences. A Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models. PCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31-1.99), ASD: aHR = 2.02 (95% CI 1.45-2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19-1.57), ASD: aHR = 1.46 (95% CI 1.21-1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys. Estimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.

Polycystic ovary syndrome and psychiatric disorders: Co-morbidity and heritability in a nationwide Swedish cohort

Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A.

Polycystic ovary syndrome: an ancient disorder?