Occurrence Of Polycystic Ovary Syndrome Research Articles

Gut microbiota in women with polycystic ovary syndrome: an individual based analysis of publicly available data

Polycystic ovary syndrome (PCOS) represents a prevalent endocrine disorder affecting numerous females worldwide. Dysbiosis of gut microbiota has been linked to the occurrence of PCOS; however, research into the characteristics of gut microbiota in PCOS patients, especially those from different regions and with different testosterone level, remains limited. Additionally, it is still unclear whether gut microbiota helps to distinguish different PCOS subtypes. We searched four electronic databases (PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov) from Jan 1, 2010 to May 1, 2024. This combined analysis included studies providing the raw data of gut microbiota in PCOS patients. We reanalyzed the characteristics of gut microbiota in PCOS patients from different regions and with different testosterone level. Fourteen publications satisfying the inclusion criteria were included in the combined analysis. Based on data from 948 individuals, we found alpha-diversity was not significantly different between PCOS and healthy control (HC) groups. However, gut microbiota composition was distinct in PCOS patients compared with healthy individuals. Specifically, Fusobacterium, Ruminococcus_gnavus_group, and Escherichia-Shigella increased, while Dysosmobacter, Schaedlerella, Merdimonas, Clostridiisalibacter, Flintibacter etal. decreased in PCOS women. Regionally, Alistipes was enriched in primarily European patients, while Blautia and Roseburia were more abundant in Chinese patients. Subtype analysis revealed that the gut microbiota of PCOS patients with higher testosterone level (PCOS-HT) differed significantly from those with lower testosterone level (PCOS-LT). Prevotella, Blautia, Dialister, Ruminococcus_torques_group and UCG-002 were enhanced in PCOS-HT patients, while Alistipes, Dysosmobacter, Phocaeicola and Faecalibacterium were diminished. Importantly, a set of eight genera effectively differentiated PCOS-HT patients from PCOS-LT patients with an AUC of 0.95. This systematic anatomization of gut microbiota revealed the microbial characteristics of PCOS patients, particularly those with different testosterone level, thus laying the foundations for further research into pathogenesis of PCOS, and the development of effective diagnostic, treatment, and intervention strategies. This work was supported by the National Natural Science Foundation of China (No. 81973217, 82260304), the Hainan Province Clinical Medical Center (QWYH202175), and the Specific Research Fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202311).

Association of SOGPI in mediating the effect of Phosphatidylcholine on polycystic Ovary Syndrome

Background Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age, marked by hormonal imbalances and disruptions in glucose and lipid metabolism. Emerging research has indicated a correlation between lipids and PCOS, yet the specific lipid profiles or associated genes identified in various studies vary, and observational data alone cannot establish causation. Therefore, our study seeks to establish a causal association between lipidome and PCOS. Methods Data from genome-wide association studies, liposomes, metabolites, and PCOS-related information were collected. Four rounds of double-sample bidirectional intermediate Mendelian Randomization analyses including liposomes to disease, liposomes to metabolites, metabolites to disease, and reverse Mendelian Randomization analysis of lipids, total effect values and intermediary effect values were calculated. The proportion mediated by the intermediary effect was determined by dividing the intermediary effect value by the total effect value. Results The analyses revealed that three liposomes and nine metabolites were causally associated with PCOS. Specifically, phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol were identified as independent risk factors for PCOS through further Mendelian Randomization analysis. The risk of developing PCOS increased by 32% for every one standard deviation increase in phosphatidylcholine and by 17% for every one standard deviation increase in 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol. Furthermore, the study revealed that phosphatidylcholine can influence the development of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol acting as a mediator, explaining 4.97% of the effect. Conclusions This study confirmed a causal relationship between phosphatidylcholine and 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol with PCOS, where phosphatidylcholine can influence the occurrence of PCOS with 1-Stearoyl-2-Oleoyl-Glycosylphosphatidylinositol as a mediator.

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.

Impact of Comorbid Polycystic Ovary Syndrome on Clinical and Laboratory Parameters in Female Adolescents with Metabolic Dysfunction-Associated Steatotic Liver Disease: A Cross-Sectional Study

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) share several pathophysiological mechanisms. While the prevalence of MASLD has been extensively studied in PCOS populations, the occurrence of PCOS among female adolescents with transient elastography (TE)-confirmed MASLD in pediatric hepatology settings remains poorly characterized. This cross-sectional study aims to address this knowledge gap and elucidate potential clinical and biochemical differences between female adolescents with MASLD and comorbid PCOS compared to those without PCOS. Methods: The study cohort included 45 female adolescents with TE-diagnosed MASLD. Comparative analyses of clinical and laboratory parameters were performed between those with (n = 19) and those without (n = 26) comorbid PCOS, diagnosed according to the Rotterdam criteria. Results: Adolescents with MASLD and comorbid PCOS exhibited significantly higher weight, lower height, and increased waist circumference compared to those without PCOS. Additionally, the prevalence of acanthosis nigricans was significantly higher in the PCOS group (68.4% versus 34.6%, p = 0.025). Regarding laboratory parameters, serum phosphorus levels and liver enzymes—including aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase—were significantly lower in adolescents with comorbid PCOS. However, no significant differences were observed in lipid profiles, glucose metabolism, or novel non-invasive biomarkers of MASLD. Conclusions: This study reveals distinct clinical and biochemical profiles in female adolescents with MASLD and comorbid PCOS compared to those without PCOS. These findings have the potential to inform and refine future screening protocols and diagnostic algorithms for these interrelated conditions, specifically tailored to pediatric hepatology settings.

Exposure to environmental doses of DEHP causes phenotypes of polycystic ovary syndrome

Globally, approximately 6–20 % of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10 mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.

Neuropeptide Network of Polycystic Ovary Syndrome - A Review.

Polycystic Ovary Syndrome (PCOS), the ubiquitous reproductive disorder, has been documented as highly prevalent (6-9%) in India. 10% of women globally are predicted to have the disease. The highly mutable endocrinopathy, with differential clinical criteria for each diagnosis of PCOS, can mask the severity of the syndrome by influencing the incidence and occurrence of PCOS. When there is a solid theoretical hypothesis between the neuroendocrine origin and ovarian origin of PCOS, recent evidence supports the neuroendocrine derivation of the pathology. It is considered of neuroendocrine basis - as it controls the ovarian axis and acts as a delicate target because it possesses receptors for various gonadal hormones, neurotransmitters & neuropeptides. Can these neuroendocrine alterations, variations in central brain circuits, and neuropeptide dysregulation be the tie that would link the pathophysiology of the disorder, the occurrence of all the 1˚ and 2˚ symptoms like polycystic ovaries, hyperandrogenism, obesity, insulin resistance, etc., in PCOS? This review anticipates providing a comprehensive overview of how neuropeptides such as Kisspeptin, Neurokinin B, Dynorphin A, β-Endorphin, Nesfatin, Neuropeptide Y, Phoenixin, Leptin, Ghrelin, Orexin, and Neudesin influence PCOS, the understanding of which may help to establish potential drug candidates against precise targets in these central circuits.

Identification of potential diagnostic genes for atherosclerosis in women with polycystic ovary syndrome

Polycystic ovary syndrome (PCOS), which is the most prevalent endocrine disorder among women in their reproductive years, is linked to a higher occurrence and severity of atherosclerosis (AS). Nevertheless, the precise manner in which PCOS impacts the cardiovascular well-being of women remains ambiguous. The Gene Expression Omnibus database provided four PCOS datasets and two AS datasets for this study. Through the examination of genes originating from differentially expressed (DEGs) and critical modules utilizing functional enrichment analyses, weighted gene co-expression network (WGCNA), and machine learning algorithm, the research attempted to discover potential diagnostic genes. Additionally, the study investigated immune infiltration and conducted gene set enrichment analysis (GSEA) to examine the potential mechanism of the simultaneous occurrence of PCOS and AS. Two verification datasets and cell experiments were performed to assess biomarkers' reliability. The PCOS group identified 53 genes and AS group identified 175 genes by intersecting DEGs and key modules of WGCNA. Then, 18 genes from two groups were analyzed by machine learning algorithm. Death Associated Protein Kinase 1 (DAPK1) was recognized as an essential gene. Immune infiltration and single-gene GSEA results suggest that DAPK1 is associated with T cell-mediated immune responses. The mRNA expression of DAPK1 was upregulated in ox-LDL stimulated RAW264.7 cells and in granulosa cells. Our research discovered the close association between AS and PCOS, and identified DAPK1 as a crucial diagnostic biomarker for AS in PCOS.

Polystyrene microplastics and di-2-ethylhexyl phthalate co-exposure: Implications for female reproductive health

Microplastics and phthalates are prevalent and emerging pollutants that pose a potential impact on human health. Previous studies suggest that both microplastics and phthalates can adversely affect the reproductive systems of humans and mammals. However, the combined impact of these pollutants on the female reproductive system remains unclear. Here we show the impacts of exposure to polystyrene microplastics (PS-MPs) and di-2-ethylhexyl phthalate (DEHP) on female Sprague-Dawley rats’ reproductive systems. We find that co-exposure to PS-MPs and DEHP results in a marked increase in cystic and atretic follicles, oxidative stress, fibrosis, and dysregulation of serum sex hormone homeostasis in the ovaries of the rats. Proteomic analysis identified differentially expressed proteins that were predominantly enriched in signaling pathways related to fatty acid metabolism and tight junctions, regulated by transforming growth factor β1 (TGF-β1). We further confirm that co-exposure to DEHP and PS-MPs activates the TGF-β1/Smad3 signaling pathway, and inhibiting this pathway alleviates oxidative stress, hormonal dysregulation, and ovarian fibrosis. These results indicate that exposure to the combination of microplastics and phthalates leads to a significant increase in atretic follicles and may increase the risk of polycystic ovary syndrome (PCOS). Our study provides new insights into the reproductive toxicity effects of microplastics and DEHP exposure on female mammals, highlighting the potential link between environmental pollutants and the occurrence of PCOS. These findings highlight the need for comprehensive assessments of the reproductive health risks posed by microplastic pollution to women and contribute to the scientific basis for evaluating such risks.

Exploring the Contribution of Traditional Medicinal Herbs in ManagingPolycystic Ovary Syndrome: A Comprehensive Review

: Polycystic ovary syndrome (PCOS) is a significant gynecological disorder that commonly affects women of reproductive age. Disturbances in the production and metabolism of androgens and estrogens mark the condition. Due to the rising occurrence of PCOS and its related physical and psychological issues, along with the role of sex hormone fluctuations in its development, the use of marketed drugs is effective in treating PCOS but is accompanied by negative consequences. Consequently, a significant number of individuals with PCOS are opting for natural remedies due to the positive therapeutic effects associated with natural medications and the constraints of allopathic treatments. This review aims to assess the impact of different herbs on alterations in sex hormone levels in the bloodstream and ovarian tissue. By conducting a comprehensive literature search utilizing databases such as PubMed, Google Scholar, and Crossref, we have gathered and analyzed pertinent information regarding the efficacy of herbal remedies in combating PCOS. Based on the available evidence, herbs consisting of phytoestrogens can potentially reduce insulin resistance, hyperandrogenism, and ovarian weight while facilitating ovulation. This review explores the importance of herbal remedies in addressing PCOS, elucidates their mechanisms of action, and examines the therapeutic uses of specific herbal medications to treat PCOS. Human studies on medicinal herbs for managing Polycystic Ovary Syndrome (PCOS) need extended durations for a comprehensive evaluation of both safety and efficacy, emphasizing the necessity for more long-term research. It is anticipated that this comprehensive review will serve as a valuable resource for researchers studying the effect of herbs on PCOS, providing them with valuable insights and information.

Exploring the Therapeutic Potential of Sodium Hydrosulfide in Alleviating Oxidative Stress and Ovarian Dysfunction in a Rat Model of Polycystic Ovary Syndrome.

Oxidative stress is known to play a key role in the occurrence of polycystic ovary syndrome (PCOS) as the most common cause of anovulatory infertility. The purpose of the current study was to investigate whether diminished activity of ovarian enzymes responsible for hydrogen sulfide (H2S) production, cystathionine β-synthase (CBS), and cystathionine γ-lyase (CSE) contributes to oxidative stress in PCOS. The study also explored whether administration of sodium hydrosulfide (NaSH), an H2S donor, could ameliorate PCOS symptoms by reducing oxidative stress. The total eighteen rats were randomly assigned into three groups (n=6): control, PCOS, and PCOS+NaSH. PCOS was induced by intramuscular injection of estradiol valerate to induce PCOS in the PCOS and PCOS+NaSH groups. The PCOS+NaSH group received 30 μmol/L of NaSH in drinking water for 27 days after PCOS induction. Ovarian tissue samples were analyzed for oxidative stress indices including malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Additional analyses measured H2S levels, CBS, and CSE activity. PCOS induction led to a significant decrease in SOD activity, H2S levels, and CBS and CSE activity, accompanied by a significant increase in MDA levels (p<0.0001). Furthermore, PCOS caused severe histological alterations in the ovaries. However, administration of NaSH effectively restored all measured parameters to pre-PCOS induction levels (p<0.0001). This study showed that the decrease in the activity of H2S-producing enzymes and H2S levels may contribute to oxidative stress in PCOS. Therefore, administration of NaSH as a H2S donor can be considered as a potential therapeutic strategy for PCOS patients.

Interleukin-1 increases SERPINE1 expression in human granulosa-lutein cell via P50/P52 signaling pathways

It has been reported that immune factors are associated with the occurrence of polycystic ovary syndrome (PCOS). Interleukin-1 (IL-1) is a member of the interleukin family that widely participates in the regulation of the inflammatory response in the immune system. In addition, it has been reported that aberrant IL-1 accumulation in serum is associated with the occurrence of PCOS. However, little is known about how IL-1 participates in the pathogenesis of PCOS. In the present study, we demonstrated that the immune microenvironment was altered in follicular fluid from PCOS patients and that the expression levels of two IL-1 cytokines, IL-1α and IL-1β were increased. Transcriptome analysis revealed that IL-1α and IL-1β treatment induced primary human granulosa-lutein (hGL) cell inflammatory response and increased the expression of serpin family E member 1 (SERPINE1). Mechanistically, we demonstrated that IL-1α and IL-1β upregulated SERPINE1 expression through IL-1R1-mediated activation of downstream P50 and P52 signaling pathways in human granulosa cells. Our study highlighted the role of immune state changes in the occurrence of PCOS and provided new insight into the treatment of patients with IL-1-induced ovarian function disorders.

Diagnosis, Management, and Associated Comorbidities of Polycystic Ovary Syndrome: A Narrative Review.

Polycystic ovary syndrome (PCOS) is the most widespread and diverse endocrine health issue affecting many adolescent-aged women globally. It is the most frequent illness in reproductive-aged women. According to the Rotterdam criteria, two out of three elements: oligo-anovulation, hyperandrogenism, and polycystic ovaries (defined as having at least one ovary with an ovarian volume > 10 mL and/or 12 or more follicles measuring 2 to 9 mm in diameter) are present in PCOS. Conducted studies show epigenetics, environmental toxins, stress, and food as external factors as well as inflammation, oxidative stress, hyperandrogenism, insulin resistance, and obesity as internal factors related to PCOS. Although a portion of the mechanism associated with the occurrence of PCOS has been identified, there is still much to learn about the exact etiology and pathophysiology. The main debate covers the best ways to diagnose and treat this disease in adolescents. Early detection is crucial because of the disease's long-term effects on metabolic and reproductive health. Before beginning treatment for this group of young women, a firm diagnosis may not be made. Various criteria are used to diagnose PCOS patients. A person with PCOS has a chance of developing several comorbidities and health effects. PCOS patients are at risk of cardiac diseases, metabolic syndromes, resistance to insulin, infertility, and many more. There are numerous medications available for PCOS therapy that need a methodical approach. However, changing one's lifestyle should come first. There is proof in the support of the usage of several medications for PCOS, including mucolytic agents, Hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitors, gliptins (oral diabetic medication), glucose-like peptide-1 receptor analogues, glitazones, and sodium-glucose cotransporter protein-2 (SGLT2) inhibitors. A comprehensive, systematic, schematic therapy approach is crucial for the treatment of PCOS.

The Impact of Polycystic Ovary Syndrome (PCOS) on the Risk of Developing Ovarian Cancer and Thyroid Disorders: A Comprehensive Review.

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects women. It is characterized by hyperandrogenism, polycystic ovarian morphology, and other related disorders. It is associated with various health conditions, such as infertility and increased risk of heart problems. Ovarian cancer is also a significant concern, as it is the fifth leading cause of death in women. While there is evidence suggesting a potential association between PCOS and ovarian cancer, the exact nature of this relationship remains unclear. Thyroid disorders, particularly hypothyroidism and Hashimoto's thyroiditis, have also been linked to PCOS. The presence of hypothyroidism can contribute to the development of polycystic ovarian morphology, affecting ovulation and hormone balance. Many works have shown a higher ubiquity of autoimmune thyroid disease in PCOS patients, indicating a potential association between the two conditions. The occurrence of PCOS, hirsutism, and acne underscores the frequency of endocrine disorders in women. This review paper examines the present relevant work on the association between PCOS and ovarian cancer as well as PCOS and thyroid disorders. A systematic literature search was conducted on the internet, such as PubMed, Scopus, and Google Scholar database, to identify peer-reviewed publications pertaining to PCOS, ovarian cancer, and thyroid disorders. While some studies have delineated a significant link between PCOS and ovarian cancer or thyroid disorders, others have yielded inconclusive results. Further research is necessary to establish a definitive causal relationship between these conditions. Understanding the relationship between PCOS, ovarian cancer, and thyroid disorders is crucial for early detection, accurate diagnosis, and effective management of these conditions. Identifying potential risk factors and developing appropriate screening strategies can improve women's health outcomes and reduce the burden associated with these disorders.

Thyroid function and polycystic ovary syndrome: a Mendelian randomization study.

Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses. The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS. Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.

Correlation between ovarian follicular development and Hippo pathway in polycystic ovary syndrome

BackgroundFor women of childbearing age, the biggest problem caused by polycystic ovary syndrome (PCOS) is infertility, which is mainly caused by anovulation, abnormal follicular development, proliferation of small antral follicles, and cystic follicles. The mechanism underlying its occurrence is not clear. The abnormal proliferation and development of follicles in PCOS patients is a complex process, which is affected by many factors. The objective of this study was to investigate the relationship between the Hippo pathway and follicular development in PCOS, and to further explore this relationship by using the YAP inhibitor verteporfin (VP).Method30 3-week-old BALB/C female rats were randomly divided into control group (n = 10), DHEA group (n = 10) and DHEA + VP group (n = 10). The morphology of ovary and the degree of follicular development were observed by HE staining, and the expression and location of AMH in ovarian follicles were observed by immunofluorescence. The ovarian reserve function index AMH, cell proliferation index PCNA and the ratio of Hippo pathway related proteins MST, LATS, YAP, P-YAP and P-YAP/YAP were detected by Western blot.ResultsAfter dividing 30 3-week-old female mice into control, dehydroepiandrosterone (DHEA; model of PCOS), and DHEA + VP groups, we found that the number of small follicles increased in the DHEA group compared to the control group. Additionally, in the DHEA group compared to the control group, anti-müllerian hormone (AMH; ovarian reserve index) increased, proliferating cell nuclear antigen (PCNA; cell proliferation index) decreased, and upstream (MST and LATS) and downstream (YAP and p-YAP) proteins in the Hippo pathway increased, though the p-YAP/YAP ratio decreased. VP ameliorated the increases in AMH, MST, LATS, YAP and p-YAP, but did not ameliorate the decrease in the p-YAP/YAP ratio.ConclusionsThis study indicates that the increased small follicles in the ovaries and changes in ovarian reserve and cell proliferation may be closely related to Hippo pathway activation. This suggests that the Hippo pathway may be an important pathway affecting the proliferation and development of follicles and the occurrence of PCOS.

#324 : Gasdermin D-Mediated Pyroptosis Underlies Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome

Background and Aims: Intestinal microflora disturbance is one of the important etiologies of polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the mechanism of macrophage pyroptosis induced by intestinal microbiota disturbance in PCOS. Method: The PCOS mouse model was established using dehydroepiandrosterone, and was studied by 16S rDNA sequencing, western blot, ELISA, GSDMD gene knockout/oral pyroptotic inhibitors, single cell transcriptomics and translatomics analysis. Results: PCOS mice showed abnormal estrous cycle, elevated serum testosterone and polycystic ovaries. Fecal 16S rDNA sequencing showed that Muribaculacea (26.76%), and Lactobacillus (40.98%) were the most abundant microbe in the intestinal tracts of control mice and PCOS mice, respectively. Difference analysis showed a significant decrease in the abundance of intestinal probiotics Akkermansia and a significant increase in Gram-negative bacteria (Desulfovibrio and Burkholderia) in PCOS mice. Intestinal microbial disturbance in PCOS mice was associated with increased serum lipopolysaccharide (LPS). LPS intraperitoneal injection can induce pyroptosis of ovarian macrophages, which also exists in the ovaries of PCOS mice. The cleavage of GSDMD protein is the final key step in pyroptosis of macrophages. GSDMD knockout ameliorated PCOS in mice. Oral administration of pyroptotic inhibitors disulfiram and metformin can increase the abundance of intestinal Akkermansia, inhibit pyroptosis of ovarian macrophages and ameliorated PCOS in PCOS group mice. Mechanically, transcriptome and translatome sequencing of primary granulosa cells showed that pyroptosis of macrophages disrupted estrogen production and promoted granulosa cell apoptosis. Conclusion: This study revealed that macrophage pyroptosis induced by intestinal flora disorder can lead to the occurrence of PCOS through granulosa cell apoptosis and estrogen synthesis dysfunction. Macrophage pyroptotic inhibitors may be a potential therapeutic strategy for PCOS.

Association of Mitochondrial Variants with the Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto's Thyroiditis.

The prevalence of Hashimoto's thyroiditis (HT) among women with polycystic ovary syndrome (PCOS) is higher than in the general female population, but the factors predisposing to the coexistence of these disorders remain unclear. This study employed whole genome sequencing of mitochondrial DNA to identify genetic variants potentially associated with the development of PCOS and HT and predisposing to their joint occurrence. A total of 84 women participated, including patients with PCOS, HT, coexisting PCOS and HT (PCOS + HT) and healthy women. Both Fisher's exact and Mann-Whitney U statistical analyses were performed to compare the frequency of variants between groups. Ten differentiating variants were common to both analyses in PCOS + HT vs. PCOS, one in PCOS + HT vs. HT, and six in PCOS + HT vs. control. Several variants differentiating the PCOS + HT group from PCOS and controls were identified, located both in the mitochondrial genes (including the MT-CYB, MT-ND1, MT-ND2, MT-ND4, MT-ND6, MT-CO1, MT-CO3) and the D-loop region. Only two variants differentiated PCOS + HT and HT groups. One variant (13237a in MT-ND5) was common for all three comparisons and underrepresented in the PCOS + HT group. Functional enrichment analysis showed 10 pathways that were unique for the comparison of PCOS + HT and PCOS groups, especially related to ATP production and oxidative phosphorylation, and one pathway, the NADH-quinone oxidoreductase, chain M/4, that was unique for the comparison of PCOS + HT and control groups. Notably, nine pathways shared commonality between PCOS + HT vs. PCOS and PCOS + HT vs. control, related to the biogenesis and assembly of Complex I. This study provides novel insights into the genetic variants associated with oxidative stress in women with coexisting PCOS and HT. Mitochondrial dysfunction and oxidative stress appear to play a role in the pathogenesis of both conditions. However, more mitochondrial variants were found to differentiate women with both PCOS and HT from those with PCOS alone than from those with HT alone.

Inflammatory and Anti-Inflammatory Parameters in PCOS Patients Depending on Body Mass Index: A Case-Control Study.

it has been suggested that chronic low-grade inflammation plays an important role in the pathogenesis of polycystic ovary syndrome (PCOS). According to previous studies, it remains unclear which cytokines influence the development of this syndrome and whether their increase is associated with the presence of excess weight/obesity or is an independent factor. The aim of our research was to determine the parameters of chronic inflammation in women with PCOS in comparison with healthy women in the normal weight and the overweight subgroups. This case-control study included 44 patients with PCOS (19 women with a body mass index (BMI) < 25 kg/m² and 25 women with a BMI ≥ 25 kg/m²) and 45 women without symptoms of PCOS (22 women with a BMI < 25 kg/m² and 23 women with a BMI ≥ 25 kg/m²). Thirty-two cytokines were analyzed in the plasma of the participants using Immunology multiplex assay HCYTA-60K-PX48 (Merck Life Science, LLC, Germany). Cytokines: interleukin-1 receptor antagonist (IL-1 RA), IL-2, IL-6, IL-17 E, IL-17 A, IL-18, and macrophage inflammatory protein-1 alpha (MIP-1 α) were increased in women with PCOS compared to controls, both in lean and overweight/obese subgroups (p < 0.05). Moreover, only lean women with PCOS had higher levels of IL-1 alpha, IL-4, IL-9, IL-12, IL-13, IL-15, tumor necrosis factor (TNF- α) alpha and beta, soluble CD40 and its ligand (SCD40L), fractalkine (FKN), monocyte-chemotactic protein 3 (MCP-3), and MIP-1 β compared to the control group (p < 0.05). IL-22 was increased in the combined group of women with PCOS (lean and overweight/obese) compared to the control group (p = 0.012). Chronic low-grade inflammation is an independent factor affecting the occurrence of PCOS and does not depend on the presence of excess weight/obesity. For the first time, we obtained data on the increase in such inflammatory parameters as IL-9, MCP-3, and MIP-1α in women with PCOS.

Alteration of Plasma Indoles in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-aged women. The occurrence of PCOS was reported to be associated with the alteration of gut microbiota. Microbiota-derived indoles may possibly play a key role in glycemic control. The purpose of this work is to reveal the alteration of plasma indoles in PCOS patients and to investigate the correlation between indoles levels and glucose metabolism. Sixty-five patients with PCOS and twenty-eight age-matched women were enrolled in this work. The concentrations of plasma indoles, including indoxyl sulfate (IS), indole-3-acetic acid (IAA), indole-3-propionate (IPA), indole (IND), and 3-methylindole (3-MI), were measured by HPLC with the fluorescence detection. The plasma levels of IS, IAA, and IND were significantly elevated in patients with PCOS compared to those in the control group (p < 0.05). Furthermore, the plasma levels of IS, IAA, and IND were positively correlated with fasting glucose, fasting insulin, and the homeostatic model of insulin resistance index (HOMA-IR) (p < 0.05). Besides, the 3-MI level in the plasma was positively correlated with the fasting glucose level, whereas plasma levels of IS, IAA, IND, and 3-MI were negatively correlated with glucagon-like peptide 1 (p < 0.05). Moreover, IS and IND were considered to be risk factors for PCOS after age, BMI, T, LH, and HOMA-IR adjustment. The area under the receiver-operating characteristic curve of the combined index of five indoles was 0.867 for PCOS diagnosis. Additionally, plasma indoles altered in PCOS, which was closely associated with the glucose metabolism.

Effect of polycystic ovary syndrome on increased risk of cardiovascular disease

Introduction and purpose: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. It is a very complex disease in which hormonal disorders result in a number of metabolic dysfunctions and malfunctioning of the ovaries. This can lead to infertility, miscarriage and an increased risk of endometrial cancer. The aim of our work is to draw attention to the influence of PCOS on increased cardiovascular risk.&#x0D; Brief description of the state of knowledge: The occurrence of PCOS, especially uncontrolled pharmacologically and non-pharmacologically, may be associated with an increased cardiovascular risk. The literature describes a higher incidence of dyslipidemia, carbohydrate metabolism disorders, obesity, hypertension, chronic inflammation and oxidative stress. As a consequence, it can lead to the development of metabolic syndrome. All these factors negatively affect the risk of developing cardiovascular disease. To prevent this, it is necessary to use appropriate pharmacological and non-pharmacological methods in women diagnosed with PCOS.&#x0D; Conclusion: The mechanism of PCOS is complex and its development is influenced by genetic, endocrine, metabolic and environmental factors. The lack of proper diagnosis and the lack of treatment of PCOS is associated with numerous metabolic complications and an increased risk of cardiovascular diseases. Due to the poorly understood pathomechanism of this disease, further long-term studies are needed to help diagnose and treat PCOS.