Etiology Of Polycystic Ovary Syndrome Research Articles

Rare variation in LMNA underlies polycystic ovary syndrome (PCOS) pathogenesis in two independent cohorts.

Polycystic ovary syndrome (PCOS) is a common, heritable endocrinopathy that is a common cause of anovulatory infertility in reproductive age women. Variants in LMNA cause partial lipodystrophy, a syndrome with overlapping features to PCOS. We tested the hypothesis that rare variation in LMNA contributes to PCOS pathogenesis and selects a lipodystrophy-like subtype of PCOS. We sequenced LMNA by targeted sequencing a discovery cohort of 811 PCOS patients and 164 healthy controls. We then analyzed LMNA from whole-exome sequencing (WES) of a replication cohort of 718 PCOS patients and 281 healthy controls. Variation in the LMNA gene, hormone and lipid profiles of participants. In the discovery cohort, we identified 8 missense variants in 15/811 cases, and 1 variant in 1/172 reproductively healthy controls. There is strong evidence for association between the variants and PCOS compared to gnomAD non-Finnish European population controls (χ2=17, p=3.7x10-5, OR=2.9). In the replication cohort, we identified 11 unique variants in 15/718 cases, and 1 variant in 281 reproductively healthy controls. Again, there is strong evidence for association with population controls (χ2=30.5, p=3.4x10-8, OR= 4.0). In both the discovery and replication cohorts, variants in LMNA identify women with PCOS with high triglycerides and extreme insulin resistance. Rare missense variation in LMNA is reproducibly associated with PCOS and identifies some individuals with lipodystrophy-like features. The overlap between this PCOS phenotype and genetic partial lipodystrophy syndromes warrants further investigation into additional lipodystrophy genes and their potential in PCOS etiology.

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.

Polycystic Ovarian Syndrome: Exploring Hypertension and Cardiometabolic Implications.

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder affecting women of reproductive age, with significant implications for cardiometabolic health. This review focuses on the relationship between PCOS and hypertension (HTN), an area that remains underexplored despite growing evidence of its importance. PCOS is characterized by hyperandrogenism (HA), ovulatory dysfunction, and polycystic ovarian morphology (PCOM), all of which contribute to a complex metabolic profile that includes insulin resistance (IR), obesity, and dyslipidemia. These factors collectively exacerbate the risk of HTN. Emerging research suggests HA in PCOS may directly influence the renin-angiotensin system (RAS), increasing blood pressure by promoting sodium retention and vascular tone. Additionally, IR, prevalent in both lean and obese women with PCOS, further contributes to HTN by enhancing sympathetic nervous system activity and impairing endothelial function. Despite these associations, the direct link between PCOS and HTN has not been definitively established, warranting further investigation. This review synthesizes current knowledge on the etiology of PCOS and its metabolic consequences, highlighting the need for targeted research to clarify the mechanisms linking PCOS with HTN. Understanding these pathways is crucial for improving the management of PCOS and reducing cardiovascular risks in affected women. By addressing these gaps, this review underscores the importance of considering HTN as a significant comorbidity in PCOS and calls for more comprehensive studies to guide clinical practice.

Women’s fertility and vitamin D: Could hypovitaminosis D biomarkers correlate with the disease, and explain the unexplained female factor infertility?

Objective: Vitamin D (Vit D) deficiency correlates women reproductive pathophysiology. We analyzed Vit D deficiency biomarkers in infertile women. Patients & method: This case-control study enrolled 80 infertile women polycystic ovary syndrome (PCOS), and other etiologies; anovulation and unexplained and 25 controls. Serum calcidiol and calcitriol were determined by ELISA and their direct ratio was calculated. Results: 72% of controls and 92.5% of patients had Vit D deficiency/insufficiency (calcidiol mean ± SDM of 33.50±22.10 vs 20.26±5.226 ng/mL and an AUC of 0.808±0.048). Calcitriol had an AUC of 0.909±0.031 that more effectively distinguished patients and etiologies (53.49±23.30 pg/mL) from controls (114.0±43.20 pg/mL; P<0.001). 4 other etiology cases and 17 controls had calcitriol levels ≥100 pg/mL. 64% of controls (4.090±0.020) and 16.25% of patients [2.634±0.855, P<0.04; 5 PCOS (3 primary/2 secondary), 3 secondary unexplained, and 5 others (one primary tubal, one primary/one secondary peritoneal, one primary/one cervical and one primary tubal had a normal ratio ≥3.333 at an AUC of 0.740±0.065. All biomarkers revealed patient levels ~50% lower than controls; lowest in PCOS and unexplained etiologies. Conclusion: Vit D levels are significantly reduced in infertile women; lowest in PCOS and unexplained etiology, for all biomarkers, where calcitriol was the optimal predictor of both infertility and etiology. Keywords: Female infertility, Polycystic ovary syndrome; unexplained infertility; Vitamin D; 25-Hydroxy-cholecalceferol, 1; 25-Dihydroxyl-cholecalceferol.

8421 The Effect of Dietary Glycotoxins on Insulin Resistance in Polycystic Ovary Syndrome

Abstract Disclosure: A. Weidner: None. K. Vann: None. J. Zhang: None. A. Roy: None. O. Astapova: None. Polycystic ovary syndrome (PCOS) is a chronic systemic disorder that affects both metabolism and reproduction. PCOS is characterized by hyperandrogenism and insulin resistance, which are closely intertwined in this disease pathophysiology. PCOS affects an estimated 10% of people with ovaries and increases risk of endometrial cancer, type 2 diabetes, and major cardiovascular events. Furthermore, treatment options are generally poorly tolerated. Despite its prevalence, severity, and enormous public health burden, the etiology of PCOS is not well-understood. Insulin resistance likely plays a central role in PCOS pathogenesis, and often leads to hyperinsulinemia as the pancreas attempts to compensate for insulin’s decreased efficacy in the body. Moreover, the Western diet is becoming increasingly rich in advanced glycation end products (AGEs): non-enzymatically modified biomolecules that have recently been found to have a harmful effect on insulin sensitivity and are associated with diabetes, aging, and oxidative stress. Serum AGE levels have been reported to be higher in both lean and obese PCOS patients, regardless of PCOS subtype. We have also found higher levels of AGE precursors in the serum of our chronic dihydrotestosterone-induced mouse model of PCOS. Using this mouse model, we have shown that ovarian granulosa cells (GCs) remain insulin-sensitive despite systemic insulin resistance and hyperinsulinemia, manifested by impaired glucose tolerance and increased HOMA-IR. To assess whether GCs respond to insulin through alternative receptor pathways, we knocked down insulin receptor in human granulosa-derived KGN cells and found that insulin-stimulated AKT phosphorylation was only minimally reduced, suggesting that insulin may signal in large part through the insulin-like growth factor 1 receptor (IGF1R) in these cells. Therefore, we believe that compensatory hyperinsulinemia plays a key role in chronic GC hyperstimulation, possibly by rerouting the insulin signal through IGF1R to overcome the resistance to insulin receptor activation, suggesting a mechanism for AGE toxicity in PCOS. We hypothesize that in PCOS, this results in impaired GC function and exacerbation of ovarian dysfunction. We will use our PCOS mouse model to study the effects of a reduced-AGE diet in ameliorating the reproductive and metabolic phenotype of an androgenized PCOS mouse. In preliminary experiments, we have found that a low-AGE diet results in lower fasting glucose in C57BL/6J mice after only 4 weeks. We expect that reproductive symptoms, such as estrous cyclicity, and metabolic symptoms, such as GTT and circulating insulin, will improve in our PCOS mouse model when mice are fed a low-AGE diet throughout development and adulthood. This project has significant clinical implications, as reducing dietary AGEs could provide an effective, tolerable, non-drug therapy option for patients with PCOS. Presentation: 6/3/2024

7869 Conditional deletion of androgen receptors from kisspeptin neurons only partially rescues the reproductive phenotype of a prenatal androgen-induced mouse model of polycystic ovary syndrome

Abstract Disclosure: A.G. Novak: None. A.V. Petriv: None. D.B. Lohr: None. K.M. Dillon: None. N.T. Neifert: None. A.M. Moore: None. Polycystic ovary syndrome (PCOS) is a prevalent cause of infertility in people with ovaries of reproductive age. Although the etiology of PCOS remains unclear, research in the clinic and with animal models suggests that hyperandrogenism (the presence of elevated circulating androgens) plays a significant role in the development of reproductive dysfunction, including irregular menstrual/estrous cycles and altered ovarian morphology. Although the site at which androgens disrupt the reproductive axis is unclear, neurons expressing kisspeptin are crucial regulators of the hypothalamic-pituitary-gonadal axis and express androgen receptors. Therefore, we hypothesize that androgen signaling at kisspeptin cells is a critical mediator of reproductive dysfunction in PCOS. To test this, we utilized Cre-lox technology to conditionally delete androgen receptors from kisspeptin cells (KARKO) in a commonly used mouse model of PCOS induced by using prenatal dihydrotestosterone treatment (prenatal androgen-treated (PNA) mice). To assess estrous cyclicity, vaginal cytology was examined daily for three weeks beginning at 50 days of age. Prenatal vehicle-treated (PNV) wild-type (WT) and PNV KARKO mice (n=6/group) exhibited regular estrous cycles with no significant differences in the percentage of time spent in proestrus, estrus, or metestrus/diestrus, indicating androgen receptors are not required to maintain fertility. As expected, PNA WT mice (n=6) rarely entered proestrus, spent significantly less time in estrus (p<0.05), and spent significantly more time in metestrus and diestrus (p<0.001) compared to the PNV groups (n=6/group, two-way ANOVA), replicating the previously reported acyclic phenotype of PNA mice. No significant differences in the percentage of time spent in cycle stages were detected between PNA WT and PNA KARKO (n=5) mice in this analysis, suggesting androgen signaling at kisspeptin cells is not required to induce acyclicity in PNA mice. Despite this acyclic phenotype, preliminary data using ovarian sections (5μm thickness) stained with hematoxylin and eosin revealed that the percentage of ovarian area composed of corpora lutea was significantly elevated in PNA KARKO mice (n=3) compared to PNA WT mice (n=4) (p<0.05, one-way ANOVA). Further, in this analysis, the area composed of corpora lutea in PNA KARKO mice was not significantly different from PNV WT and KARKO controls (n=6/group), suggesting PNA KARKO mice exhibit a comparable ovulation rate to fertile controls. Together, these data show that androgen signaling at kisspeptin cells partially contributes to the development of anovulation in PNA mice. However, additional mechanisms likely contribute to developing the full PCOS-like reproductive phenotype. Presentation: 6/1/2024

Research on the genetic etiology of polycystic ovary syndrome in the post-GWAS era

Great progress has been made in the genetic research of PCOS, thanks to the application of genome association study (GWAS) technology. However, in the post-GWAS era, investigating the pathogenic mechanisms related to numerous genetic loci has become challenging, leading to the current generalized approach to treating PCOS. To address this issue, taking the significantly associated susceptibility gene THADA as an example, we share a series of advancements from the perspectives of genetic evolution, epigenetics, and gene function studies. Our aim is to provide guidance for a better understanding of the essence of PCOS.

Transcriptome Analysis of Mesenchymal Progenitor Cells Revealed Molecular Insights into Metabolic Dysfunction and Inflammation in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a female endocrine disorder with metabolic issues. Hyperandrogenism combined with hyperinsulinemia exacerbates the reproductive, metabolic, and inflammatory problems in PCOS patients. The etiology of PCOS is unclear. Patient-specific induced pluripotent stem cells (iPSCs) offer a promising model for studying disease mechanisms and conducting drug screening. Here, we aim to use mesenchymal progenitor cells (MPCs) derived from PCOS iPSCs to explore the mechanism of PCOS. We compared the transcriptome profiles of PCOS and healthy control (HC) iPSC-derived MPCs (iPSCMs). Moreover, we assess the impact of androgens on iPSCMs. In the comparison between PCOS and HC, the expression levels of 1026 genes were significantly different. A gene set enrichment analysis (GSEA) revealed that adipogenesis- and metabolism-related genes were downregulated, whereas inflammation-related genes were upregulated in the PCOS iPSCMs. Dysregulation of the TGF-β1 and Wnt signaling pathways was observed in the PCOS iPSCMs. Furthermore, there was impaired adipogenesis and decreased lipolysis in the PCOS iPSCMs-derived adipocytes. With testosterone treatment, genes related to metabolism were upregulated in the HC iPSCMs but downregulated in the PCOS iPSCMs. The impact of testosterone varied among HCs and PCOS iPSCMs, possibly because of a genetic predisposition toward PCOS. This study found specific signaling pathways that could serve as therapeutic targets for PCOS.

Development of an Endoplasmic Reticulum Stress-Related Diagnostic Signature in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder in premenopausal women. This investigation was to elucidate the underlying mechanism of endoplasmic reticulum stress (ERS) activation in granulosa cells, which has been implicated in the etiology of PCOS. Differentially expressed genes (DEGs) between PCOS and control groups were integrated with ERS gene lists from databases to identify DE-ERS genes, and functional analyses were performed. Univariate regression analysis and the LASSO method were used to select diagnostic factors, followed by establishing a DE-ERS gene-based diagnostic model. A nomogram model was further generated to predict the risk of PCOS. The correlation between ERS gene expression and immune cell proportion was assessed. A total of 14 DE-ERS genes associated with "protein processing in endoplasmic reticulum", "ferroptosis", and "glycerophospholipid metabolism" were selected as PCOS-related factors. An eight-DE-ERS genes-based diagnostic model was developed and displayed satisfactory performance in the training (Area under curve (AUC) = 0.983) and validation datasets (AUC = 0.802). High risk of PCOS can be accurately predicted, which might contribute to clinical decision-making. Moreover, EDEM1 expression was significantly positively correlated with naive B cell infiltration, while PDIA6 was negatively correlated with neutrophil proportion (P < 0.001). We identified eight novel molecules and developed an ERS gene-based diagnostic model in PCOS, which might provide novel insight for finding biomarkers and treatment methods.

Progress of Chinese and Western Medicine Research on Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common clinical disease of reproductive endocrine hormone abnormalities and metabolic disorders, with a variety of clinical symptoms and complex etiology. Recent studies have shown that genetics, reproductive endocrine hormones, inflammatory factors, intestinal flora, microRNAs, signal transduction pathways and insulin resistance are closely related to the development of PCOS. Regarding the treatment modalities of PCOS, Western medicine mostly focuses on symptomatic treatment for elevated androgens, ovulation abnormalities, menstrual irregularities and insulin resistance. Chinese medicine focuses on conditioning, and adopts Chinese medicine, acupuncture and needle-medicine combination for different identification and typing through the idea of holistic view. The combination of Chinese and Western medicine gives full play to the advantages between modern medicine and traditional medicine, and combines Western medicine with Chinese medicine for symptomatic treatment, which is a holistic approach and has significant therapeutic effects. Therefore, this paper provides an overview of the research on the etiology and pathogenesis of PCOS in recent years, as well as an overview of the treatment of PCOS by Western medicine, Chinese medicine and the combination of Chinese and Western medicine.

The Utility of SHBG Assay in Clinical Biochemistry for Iraqi Women

Polycystic ovarian syndrome, additionally called PCOS is the most widespread endocrine illness amongst women. The aetiology of PCOS is attributed to a multi-factorial interplay among environmental and genetic effects. The overarching goal evaluates the correlation among blood concentrations of total testosterone, sex-hormone-binding globulin (SHBG), estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in ladies with PCOS and the impact of obesity, age, marital popularity on the obtained results. This study was conducted at the National Center for Educational Laborites /Medical City/ Baghdad. The study comprised of a sample of 83 women, elderly between 17 -45 years, who had been selected in a random manner from a Gynaecology Clinic. The statistics collection duration spanned from November 2022 to March 2023. Women with polycystic ovary syndrome (PCOS) were based on their body mass index (BMI), age and marital status. Investigations included serum-free testosterone measurements by enzyme-linked immune sorbent assay (ELISA), total testosterone, SHBG, E2, FSH and LH by Automated Immunoassay Analyzer (AIA-2000). The current findings showed non-significant distinctions in mean values of BMI between studied groups of patients and controls which reflect matches between them. This study revealed the effect of marital status compared to PCOS and healthy control subjects. Married PCOS patients were non significantly affected (83.9% vs. 85.2%, p&gt;0.05) as compared to married controls. Results of these studies showed a significantly higher mean rate of serum FSH level in PCOS-affected women when opposed to normal individuals.

Epigenetic/circadian clocks and PCOS.

Polycystic ovary syndrome (PCOS) affects 6-20% of reproductive-aged women. It is associated with increased risks of metabolic syndrome, Type 2 diabetes, cardiovascular diseases, mood disorders, endometrial cancer and non-alcoholic fatty liver disease. Although various susceptibility loci have been identified through genetic studies, they account for ∼10% of PCOS heritability. Therefore, the etiology of PCOS remains unclear. This review explores the role of epigenetic changes and modifications in circadian clock genes as potential contributors to PCOS pathogenesis. Epigenetic alterations, such as DNA methylation, histone modifications, and non-coding RNA changes, have been described in diseases related to PCOS, such as diabetes, cardiovascular diseases, and obesity. Furthermore, several animal models have illustrated a link between prenatal exposure to androgens or anti-Müllerian hormone and PCOS-like phenotypes in subsequent generations, illustrating an epigenetic programming in PCOS. In humans, epigenetic changes have been reported in peripheral blood mononuclear cells (PBMC), adipose tissue, granulosa cells (GC), and liver from women with PCOS. The genome of women with PCOS is globally hypomethylated compared to healthy controls. However, specific hypomethylated or hypermethylated genes have been reported in the different tissues of these women. They are mainly involved in hormonal regulation and inflammatory pathways, as well as lipid and glucose metabolism. Additionally, sleep disorders are present in women with PCOS and disruptions in clock genes' expression patterns have been observed in their PBMC or GCs. While epigenetic changes hold promise as diagnostic biomarkers, the current challenge lies in distinguishing whether these changes are causes or consequences of PCOS. Targeting epigenetic modifications potentially opens avenues for precision medicine in PCOS, including lifestyle interventions and drug therapies. However, data are still lacking in large cohorts of well-characterized PCOS phenotypes. In conclusion, understanding the interplay between genetics, epigenetics, and circadian rhythms may provide valuable insights for early diagnosis and therapeutic strategies in PCOS in the future.

Polycystic Ovary Syndrome, Insulin Resistance, and Cardiovascular Disease.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. It has been associated with metabolic, reproductive, and psychiatric disorders. Despite its association with insulin resistance (IR) and cardiovascular disease (CVD) risk factors, the association between PCOS and CVD outcomes has been conflicting. This review reports the updated evidence between PCOS, insulin resistance, and CVD events. IR is highly prevalent occurring in 50 to 95% of general and obese PCOS women. The etiology of PCOS involves IR and hyperandrogenism, which lead to CVD risk factors, subclinical CVD, and CVD outcomes. Multiple studies including meta-analysis confirmed a strong association between PCOS and CVD events including ischemic heart disease, stroke, atrial fibrillation, and diabetes, particularly among premenopausal women, and these associations were mediated by metabolic abnormalities. PCOS is highly familial and has substantial CVD risk and transgenerational effects regardless of obesity. A personalized approach to the CVD risk assessment and management of symptom manifestations should be conducted according to its phenotypes. Lifestyle modifications and reduction in environmental stressors should be encouraged for CVD prevention among PCOS women.

Role of the gut microbiota and innate immunity in polycystic ovary syndrome: Current updates and future prospects.

Polycystic ovary syndrome (PCOS) is one of the modern intractable reproductive diseases. The female irregular menstruation, infertility, obesity, and so forth caused by PCOS have become a hot issue affecting family harmony and social development. The aetiology of PCOS is complex. In recent years, many scholars have found that its pathogenesis was related to the imbalance of gut microbiota. Gut microbiota can form two-way communication with the brain through the 'gut-brain axis' and affect the host's metabolism. Current research has confirmed that the gut microbiota can interfere with glucose and lipid metabolism, insulin sensitivity, hormone secretion and follicular development in women by altering intestinal mucosal permeability and secreting metabolites. In addition, the diversity and composition of gut microbiota of PCOS patients changed, which may affect the metabolic function of the gut microbiota and the ability to produce metabolites, and may also directly or indirectly affect the endocrine function. This study reviewed recent research advances about the role of gut microbiota in PCOS. In order to provide basis for prevention and treatment of PCOS based on gut microbiota.

Novel biomarkers in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is an alarming gynaecological endocrine disorder affects women of reproductive age. Hyperandrogenism contributes for a cluster of cardio-metabolic risk factors characterized by reproductive dysfunction, polycystic ovaries, anovulation, and cosmetic dysfunctions. Although during the past decades, substantial research efforts tried to uncover the exact aetiology and pathogenesis of PCOS but owing to the complex etiology, the patho-physiological mechanisms of PCOS remains in doubt. To develop potential and highly efficient therapeutic strategies, there are many proteins which can act as potential biomarkers for PCOS. These biomarker proteins and enzymes may involve in the early detection and handling of this condition and mitigate the risk of long-term problems.

Trehalosemodulates OVRAS to improve oxidative stress and apoptosis in KGN cells and ovaries of PCOS mice

The etiology of polycystic ovary syndrome (PCOS) is complex and variable, and there is no exact cause or good treatment method. Most of the methods of hormones are used to temporarily meet the needs of patients. Experimental evidence has shown that trehalose has, anti-apoptotic, anti-oxidative, glucose-lowering, and insulin resistance effects. However, whether trehalose has a therapeutic effect on PCOS is unknown. It has been reported that the ovarian renin-angiotensin system (OVRAS) is involved in the development of PCOS, but it has not been fully elucidated. This study aims to explore the effect of trehalose on PCOS and elucidate the related OVRAS mechanism. We first observed that body weight, estrous cycle, ovarian follicles at all levels, glucose tolerance, serum hormones, and insulin resistance were improved by trehalose treatment in the PCOS mouse model. Moreover, trehalose treatment also ameliorated ovarian oxidative stress and apoptosis in PCOS mice, as determined by TUNNEL apoptosis staining, total SOD in ovarian homogenate, and WB assay. OVRAS mainly involves two classic pathways, namely the ACE/AngII/AT1R/AT2R, and ACE2 / Ang1-7/ MASR, Which play different functions. In PCOS mouse ovaries, we found that ACE/AngII/AT1R was up-regulated and ACE2/Ang1-7/MASR and AT2R were down-regulated by PCR and WB experiments, However, trehalose treatment changed its direction. In addition, we also found that trehalose ameliorated DHEA-induced oxidative stress and apoptosis in KGN by PCR and WB experiments, mainly by down-regulating ACE/AngII/AT1R. Our study shows that trehalose improves symptoms of PCOS mainly by down-regulating ACE/AngII/AT1R, revealing a potential therapeutic target for PCOS.

Prevalence of Polycystic Ovarian Syndrome (PCOS) Like Symptoms in the General Practice of an Obstetrics and Gynecological Office on the Island of Tobago: A Retrospective Chart Analysis

Introduction: Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies found in reproductive age women. It is characterized by anovulatory infertility, menstrual dysfunction, and hirsutism. It is thought to be associated with an increased risk of metabolic aberrations, including insulin resistance, hyperinsulinism and type 2 diabetes mellitus (T2D). Due to the racial disparities associated with insulin resistance and T2D, we hypothesized that the prevalence of PCOS like symptoms would be increased on the island of Tobago where women were predominantly of Afro-Caribbean descent. Study Design: A retrospective chart review of 1000 women seen in an obstetrics and gynecological office over a 7-year period was conducted. Inclusion criteria included race, body mass index (BMI)&lt;50, and no diagnosis of a co-morbid endocrinopathy. Of the 1000 women, 884 Afro-Caribbean women were included in the analysis. PCOS diagnosis was made based on clinical signs and symptoms verified on ultrasound. The diagnosis was considered if a patient presented with ≥2 of the following signs and symptoms: infertility after &gt;1yr of unprotected sex; irregular menses with periods &gt;35 d, &lt;21 d or &lt;6/yr; overweight/ obese (BMI&gt;25); hirsutism; and acne. Results: Within the study population, 15.7% of participants had irregular menses, 9.2% had infertility, 4.0% had hirsutism and 0.4% developed acne. The prevalence of PCOS based on clinical diagnoses and ultrasonographic evidence was 19.7%. No statistical difference (p&lt;0.05) was found between the two groups with regards to BMI, age and parity. When stratified by age, differences in infertility were found in the 20-24 and 35-39 year old age groups with rates at 10.5 v 18.9% and 15.4 v. 30.2%, respectively. The incidence of irregular menses also differed among age groups, with PCOS patients reporting significantly higher percentages between 30-50%. Conclusion: PCOS appears to be a common disorder on the island of Tobago with a prevalence of 19.7%. This prevalence is higher than in North American studies but is in line with data excluding biochemical analysis. As PCOS is a heterogeneous disorder with diverse phenotypes and probable ethno-genetic variations, the next step would be to further characterize the characteristics of PCOS in the Tobago population. This includes obtaining a full battery of biochemical profiles of women diagnosed with PCOS-like symptoms and the consideration of gene environment interactions including exposure to endocrine disruptors thought to be involved in the etiology of PCOS.

Plant medicine metabolite Yulinzhu treating neurological disorder causing polycystic ovary syndrome: a systematic review and a meta-analysis.

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder that affects women of reproductive age, characterized by chronic anovulation, hyperandrogenism, and polycystic ovarian morphology. Emerging evidence indicates that neurological disorders play a significant role in the etiology of PCOS, highlighting the complex interplay between the central nervous system (CNS) and ovarian function. Yulinzhu, a traditional Chinese medicine (TCM) formulation, has been traditionally used to regulate menstrual cycles and improve fertility. This study aims to investigate the efficacy and mechanisms of Yulinzhu in treating PCOS induced by neurological disorders. An extensive literature search was performed across electronic databases such as PubMed, EMBASE, Cochrane Library, and China National Knowledge Infrastructure (CNKI), covering publications up to 1 June 2024. The review included randomized controlled trials (RCTs) that compared Yulin Zhu with placebo, standard care, or other active treatments in patients with PCOS. Two reviewers independently carried out data extraction and quality assessment. Meta-analyses were conducted using both fixed and random-effects models, with heterogeneity evaluated using the I2 statistic. We screened 891 records and included 6 studi es in the meta-analysis. The meta-analysis revealed that Yulinzhu about effective rate [RR = 1.19, 95% CI (1.10, 1.29), p < 0.0001], pregnancy rate [RR = 2.80, 95% CI (1.65, 4.76), p < 0.0001] and ovulation rate [RR = 1.33, 95% CI (1.10, 1.62), p = 0.04]. Meta-analysis shows the results of follicle estrogen [WMD = 0.69, 95% CI (-0.39, 1.78), p = 0.21], luteinizing hormone [WMD = -2.27, 95% CI (-3.86, -0.67), p = 0.005], testosterone [WMD = -0.44, 95% CI (-0.64, -0.25), p < 0.0001], estradiol [WMD = 16.20, 95% CI (2.74, 29.67), p < 0.0001]. This study demonstrates that plant medicine compund Yulinzhu may effectively treats PCOS including hormonal regulation, anti-inflammatory actions, and neuroprotection. We expect further research with larger, well-designed clinical trials to substantiate our conclusions.

The epoxiconazole and tebuconazole fungicides impair granulosa cells functions partly through the aryl hydrocarbon receptor (AHR) signalling with contrasted effects in obese, normo-weight and polycystic ovarian syndrome (PCOS) patients

Polycystic ovarian syndrome (PCOS), frequently associated to obesity, is the main reproductive disorder in women in age to procreate. Some evidence suggests that pesticides can result in alterations of the female reproductive system, including polycystic ovary syndrome (PCOS). Here, we detected two fungicides, Tebuconazole (Tb) and Epoxiconazole (Epox) in the soils and waters of French area. Our hypothesis is that these two triazoles could be associated to the etiology of PCOS. We used the human KGN cell line and primary human granulosa cells (hGCs) from different group of patients: normal weight non PCOS (NW), normal weight PCOS (PCOS NW), obese (obese) and obese PCOS (PCOS obese). We exposed in vitro these cells to Tb and Epox from 0 up to 10 mM for 24 and 48 h and analysed cell viability and steroidogenesis. In hGCs NW, cell viability was reduced from 12.5 µM for Tb and 75 µM for Epox. In hGCs NW, Epox decreased progesterone (Pg) and estradiol (E2) secretions and inhibited STAR, HSD3B and CYP19A1 mRNA expressions from 25 µM and increased AHR mRNA expression from 75 µM. Tb exposure also reduced steroid secretion and STAR and CYP19A1 mRNA expressions and increased AHR mRNA expression but at cytotoxic concentrations. Silencing of AHR in KGN cells reduced inhibitory effects of Tb and Epox on steroid secretion. Tb and Epox exposure decreased more steroid secretion in hGCs from obese, PCOS NW and PCOS obese groups than in NW group. Moreover, we found a higher gene expression of AHR within these three groups. Taken together, both Epox and Tb reduced steroidogenesis in hGCs through partly AHR and Tb was more cytotoxic than Epox. These triazoles alter more strongly PCOS and/or obese hGCs suggesting that human with reproductive disorders are more sensitive to triazoles exposure.

Relationships between nonalcoholic fatty liver disease and polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) and non-alcoholic fatty liver disease (NAFLD) are two common non-infectious pathologies. Their frequency and medico-social significance have increased significantly over the past decades and reflect the effects of radical changes in human lifestyle on human health in a transgenerational aspect. Due to absence a complete understanding of the etiology and pathogenesis of PCOS and NAFLD, modern medicine still does not have etiopathogenetic methods of treating these frequent diseases. Considering epidemiological and pathogenetic data PCOS and NAFLD can be regarded as related pathologies, which creates the prospect of improving the effectiveness of their management if the joint approach to scientific research and implementation of their results in medical practice is applied.The purpose of the review is to summarize the current scientific data on the common pathophysiological and clinical relationships between PCOS and NAFLD, which can contribute to improving the effectiveness management of both diseases.Pathogenetic relationships between PCOS and NAFLD are bidirectional. According to current data, it seems possible to consider PCOS as a significant risk factor for the development of NAFLD in women of reproductive age both in the presence of excess weight and with normal body weight.As is known, that liver is involved in the clearance of androgens by the formation of sex steroid-binding globulin, as well as in the inactivation of insulin. Disruption of these metabolic processes due to liver pathology can lead to the development or strengthening of biochemical and clinical hyperandrogenism and the development of hyperinsulinemia and insulin resistance (IR).Conclusions. The presence of fatty liver and especially steatohepatitis deepens the hormonal disorders inherent in PCOS (primarily, an increase of free androgens, IR and ovulatory dysfunction), as well as potentiates and accelerates the development of cardiometabolic complications, including atherogenic dyslipidemia, dysglycemia, metabolic syndrome and cardiovascular complications. Early detection of NAFLD in women with PCOS, regardless of the presence of obesity, may improve the effectiveness of PCOS management and prevention of its cardiometabolic risks.