Mechanism Of Polycystic Ovary Syndrome Research Articles

Effect of berberine combined with metformin on autophagy in polycystic ovary syndrome by regulating AMPK/AKT/mTOR pathway.

The pathologic mechanism of polycystic ovary syndrome (PCOS) is related to increased autophagy of granulosa cells. Both berberine and metformin have been shown to improve PCOS, but whether the combination of berberine and metformin can better improve PCOS by inhibiting autophagy remains unclear. PCOS models were constructed by injecting dehydroepiandrosterone into rats, and berberine, metformin or berberine combined with metformin was administered to rats after modeling. Rats' body weight and ovarian weight were measured before and after modeling. Histopathological examination of ovarian tissue and estrous cycle analysis of rats were performed. Insulin resistance, hormone levels, oxidative stress, and lipid metabolism in PCOS rats were assessed. Expression of the AMPK/AKT/mTOR pathway and autophagy-related proteins was analyzed by Western blot assays. Granulosa cells were isolated from rat ovarian tissue and identified by immunofluorescence staining followed by transmission electron microscopy analysis. Berberine combined with metformin reduced the body weight and ovarian weight of PCOS rats, increased the number of primordial and primary follicles, decreased the number of secondary and atretic follicles, normalized the estrous cycle, and improved insulin resistance, androgen biosynthesis, oxidative stress and lipid metabolism disorders, and increased estrogen production. In addition, berberine combined with metformin reduced the number of autophagosomes in granulosa cells, which may be related to AMPK/AKT/mTOR pathway activation, decreased Beclin1 and LC3II/LC3I levels, and increased p62 expression. Berberine combined with metformin could inhibit autophagy by activating the AMPK/AKT/mTOR pathway in PCOS, indicating that berberine combined with metformin is a potential treatment strategy for PCOS.

P-604 Underlying molecular mechanisms of Polycystic Ovary Syndrome and Morphology: focusing on the ovary

Abstract Study question What mechanisms are involved in the ovarian alterations of Polycystic Ovary Syndrome (PCOS) and Morphology? Summary answer PCOS patients associated a distinctive impairment of oxidative phosphorylation and dysregulated complement system in their follicular compartments not found in Polycystic Ovarian Morphology (PCOM) women. What is known already PCOS is a major cause of female infertility characterized by aberrant follicular development and hormonal imbalances leading to reproductive symptoms such as anovulation, poor oocyte quality, and hyperandrogenism. Likewise, PCOM is present in 16-25% of women with regular menses, but the clinical relevance of this ovarian phenotype and its correlation with PCOS remains unclear. Therefore, to establish the specific molecular mechanisms underlying the ovarian alterations in PCOS using High-throughput techniques will allow us to provide a better clinical management and a differential diagnosis with PCOM women. Study design, size, duration Cross-sectional molecular study including samples from 26 patients undergoing an IVF cycle between 2019-2022 at Hospital La Fe (Valencia, Spain). Eight women were considered PCOS, eleven PCOM and seven were control fertile patients. Granulosa cells (GCs) and follicular fluid (FF) samples were obtained during oocyte retrieval to perform RNA-seq and proteomic analysis, respectively. Participants/materials, setting, methods Women with two or more Rotterdam-criteria were considered as PCOS, while PCOM was defined by polycystic ovarian morphology on ultrasound with regular ovulatory cycles. RNA from GCs was obtained and sequenced using NextSeq500-Illumina to identify differentially expressed genes (DEGs) using DESeq2 (R-software). The proteome of FF samples was established by LC-MS/MS and differentially expressed proteins (DEPs) analyzed with limma package. Functional enrichment analysis of DEGs and DEPs (FDR< 0.05) was performed based on KEGG database. Main results and the role of chance RNA-seq data revealed clear distinctions between GCs from PCOS and control women, with 526 DEGs. By contrast, the transcriptomes of PCOS and PCOM were more similar, with only 34 DEGs. Notably, oxidative phosphorylation emerged as the most enriched pathway in both comparisons, showing a differential expression in PCOS. Indeed, 6 out of 12 shared DEGs (MT-TP, MT-ND4L, MT-ND2, MT-ATP8, MT-ND4, and MT-ATP6), were mitochondrial genes found upregulated in PCOS vs. PCOM and control samples. These findings suggest that granulosa cells from PCOS present a dysregulation in oxidative phosphorylation, potentially linked to alterations in those genes associated with the mitochondrial electron transport chain. The proteomic analysis showed 37 DEPs in the FF of PCOS compared with controls, being these DEPs mainly involved in the complement and coagulation cascades, PI3K-AKT pathway, oocyte meiosis and ferroptosis. Furthermore, the PCOS vs. PCOM analysis revealed 42 DEPs, significantly enriched also in complement and coagulation cascades, ferroptosis and glutathione metabolism. Interestingly, fifteen proteins were differentially expressed in both comparisons, with four of them related to the complement system (PROS1, C1S, C1QB and MASP2), suggesting that an alteration in this system at follicular fluid level might be one of the hallmarks of PCOS. Limitations, reasons for caution Further experimental studies are required to validate the specific changes identified in our study. Moreover, to establish how these alterations in the follicular compartments affect the oocytes of PCOS patients should also be explored. Wider implications of the findings Our study focused on specific mechanisms involved in PCOS ovarian alterations, providing new insights into potential biomarkers for an accurate diagnosis and management of this pathology. Dysregulations in oxidative phosphorylation and complement system might play a crucial role in PCOS multifactorial nature, contributing to impaired folliculogenesis and decreased oocyte quality. Trial registration number Not Applicable

The Novel Insight of Gut Microbiota from Mouse Model to Clinical Patients and the Role of NF-κB Pathway in Polycystic Ovary Syndrome.

Polycystic Ovary Syndrome (PCOS) is a metabolic disorder characterized by hyperandrogenism and related symptoms in women of reproductive age. Emerging evidence suggests that chronic low-grade inflammation plays a significant role in the development of PCOS. The gut microbiota, a complex bacterial ecosystem, has been extensively studied for various diseases, including PCOS, while the underlying mechanisms are not fully understood. This review comprehensively summarizes the changes in gut microbiota and metabolites observed in PCOS and their potential association with the condition. Additionally, we discuss the role of abnormal nuclear factor κB signaling in the pathogenesis of PCOS. These findings offer valuable insights into the mechanisms of PCOS and may pave the way for the development of control and therapeutic strategies for this condition in clinical practice. By bridging the gap between mouse models and clinical patients, this review contributes to a better understanding of the interplay between gut microbiota and inflammation in PCOS, thus paving newways for future investigations and interventions.

Immune and oxidative stress disorder in ovulation-dysfunction women revealed by single-cell transcriptome.

Ovulation dysfunction is now a widespread cause of infertility around the world. Although the impact of immune cells in human reproduction has been widely investigated, systematic understanding of the changes of the immune atlas under female ovulation remain less understood. Here, we generated single cell transcriptomic profiles of 80,689 PBMCs in three representative statuses of ovulation dysfunction, i.e., polycystic ovary syndrome (PCOS), primary ovarian insufficiency (POI) and menopause (MENO), and identified totally 7 major cell types and 25 subsets of cells. Our study revealed distinct cluster distributions of immune cells among individuals of ovulation disorders and health. In patients with ovulation dysfunction, we observed a significant reduction in populations of naïve CD8 T cells and effector memory CD4 T cells, whereas circulating NK cells and regulatory NK cells increased. Our results highlight the significant contribution of cDC-mediated signaling pathways to the overall inflammatory response within ovulation disorders. Furthermore, our data demonstrated a significant upregulation of oxidative stress in patients with ovulation disorder. Overall, our study gave a deeper insight into the mechanism of PCOS, POI, and menopause, which may contribute to the better diagnosis and treatments of these ovulatory disorder.

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.
 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.
 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.

The characteristics of gut microbiome in PCOS patients with overweight/obesity individuals

Objective: Polycystic ovary syndrome (PCOS) is one of the most common reproductive and endocrine disorders in women of reproductive age. More than 80% of PCOS patients are overweight/obese. However, the mechanism of PCOS and its combined overweight/obesity remains unclear. Recent studies have found that gut microbiota may be involved in the development of PCOS. This study investigates the characteristics of gut microbiota in overweight/obese PCOS patients.

Shared diagnostic genes and potential mechanism between PCOS and recurrent implantation failure revealed by integrated transcriptomic analysis and machine learning.

Polycystic ovary syndrome (PCOS) is a complex endocrine metabolic disorder that affects 5-10% of women of reproductive age. The endometrium of women with PCOS has altered immune cells resulting in chronic low-grade inflammation, which attribute to recurrent implantation failure (RIF). In this study, we obtained three PCOS and RIF datasets respectively from the Gene Expression Omnibus (GEO) database. By analyzing differentially expressed genes (DEGs) and module genes using weighted gene co-expression networks (WGCNA), functional enrichment analysis, and three machine learning algorithms, we identified twelve diseases shared genes, and two diagnostic genes, including GLIPR1 and MAMLD1. PCOS and RIF validation datasets were assessed using the receiver operating characteristic (ROC) curve, and ideal area under the curve (AUC) values were obtained for each disease. Besides, we collected granulosa cells from healthy and PCOS infertile women, and endometrial tissues of healthy and RIF patients. RT-PCR was used to validate the reliability of GLIPR1 and MAMLD1. Furthermore, we performed gene set enrichment analysis (GSEA) and immune infiltration to explore the underlying mechanism of PCOS and RIF cooccurrence. Through the functional enrichment of twelve shared genes and two diagnostic genes, we found that both PCOS and RIF patients had disturbances in metabolites related to the TCA cycle, which eventually led to the massive activation of immune cells.

Weighted Gene Co-Expression Network Analysis (WGCNA) Discovered Novel Long Non-Coding RNAs for Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) affects reproductive-age women. This condition causes infertility, insulin resistance, obesity, and heart difficulties. The molecular basis and mechanism of PCOS might potentially generate effective treatments. Long non-coding RNAs (lncRNAs) show control over multifactorial disorders' growth and incidence. Numerous studies have emphasized its significance and alterations in PCOS. We used bioinformatic methods to find novel dysregulated lncRNAs in PCOS. To achieve this objective, the gene expression profile of GSE48301, comprising PCOS patients and normal control tissue samples, was evaluated using the R limma package with the following cut-off criterion: p-value < 0.05. Firstly, weighted gene co-expression network analysis (WGCNA) was used to determine the co-expression genes of lncRNAs; subsequently, hub gene identification and pathway enrichment analysis were used. With the defined criteria, nine novel dysregulated lncRNAs were identified. In WGCNA, different colors represent different modules. In the current study, WGCNA resulted in turquoise, gray, blue, and black co-expression modules with dysregulated lncRNAs. The pathway enrichment analysis of these co-expressed modules revealed enrichment in PCOS-associated pathways, including gene expression, signal transduction, metabolism, and apoptosis. In addition, CCT7, EFTUD2, ESR1, JUN, NDUFAB1, CTTNB1, GRB2, and CTNNB1 were identified as hub genes, and some of them have been investigated in PCOS. This study uncovered nine novel PCOS-related lncRNAs. To confirm how these lncRNAs control translational modification in PCOS, functional studies are required.

Posttranslational modifications in pathogenesis of PCOS.

Polycystic ovary syndrome (PCOS) is a lifelong reproductive, metabolic, and psychiatric disorder that affects 5-18% of women, which is associated with a significantly increased lifetime risk of concomitant diseases, including type 2 diabetes, psychiatric disorders, and gynecological cancers. Posttranslational modifications (PTMs) play an important role in changes in protein function and are necessary to maintain cellular viability and biological processes, thus their maladjustment can lead to disease. Growing evidence suggests the association between PCOS and posttranslational modifications. This article mainly reviews the research status of phosphorylation, methylation, acetylation, and ubiquitination, as well as their roles and molecular mechanisms in the development of PCOS. In addition, we briefly summarize research and clinical trials of PCOS therapy to advance our understanding of agents that can be used to target phosphorylated, methylated, acetylated, and ubiquitinated PTM types. It provides not only ideas for future research on the mechanism of PCOS but also ideas for PCOS treatments with therapeutic potential.

Микронутриентная поддержка репродуктивной функции при синдроме поликистозных яичников, осложненном метаболическими рисками

There are currently no registered medications with polycystic ovary syndrome (PCOS) among the indications. Synergistic and pathogenetically sound micronutrient support in women’s reproductive health with an efficient choice of compounds can have an impact on all pathogenic mechanisms of PCOS: insulin resistance, systemic inflammation, oxidative stress, regulation of the gonadotropin ratio (luteinizing hormone / follicle stimulating hormone) and levels of active androgens. Myo-Inositol in patients with PCOS improves ovarian function and increases fertility, reduces the severity of hyperandrogenism, including acne and hirsutism, positively affects metabolic aspects by reducing insulin resistance; modulates hormonal parameters involved in reproductive function and ovulation. Experimental studies show the possibility of improving oocyte morphology and embryo quality with Myo-Inositol in combination with folic acid (FA). Combination therapy with FA and Myo-Inositol prevents the formation of congenital anomalies through epigenetic effects on DNA methylation. Vitamin D supplementation leads to the reduction in insulin resistance and hyperandrogenism, contributes to the production of progesterone in the ovaries. Vitamin D has a protective effect on cells in the development of insulin resistance due to its own anti-inflammatory effect. Epigallocatechin-3-gallate (EGCG) is a natural antioxidant compound of flavonoids. Chromium promotes glucose absorption and is involved in carbohydrate, protein, and lipid metabolism. Synergism of these compounds leads to a clinically significant effect on metabolic and hormonal parameters, which can be used in patients with current and delayed reproductive plans, as well as in the group of women who are treated for infertility by assisted reproductive technologies. Key words: Myo-Inositol, folic acid, vitamin D, epigallocatechin gallate, chromium, insulin resistance, polycystic ovary syndrome, reproductive function

Cysteine-Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice.

Polycystic ovary syndrome (PCOS), which affects 5–10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine–cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.

High-Throughput Sequencing Profiles About lncRNAs and mRNAs of Ovarian Granulosa Cells in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, which is characterized by ovulatory dysfunction, clinical and/or biochemical androgen excess, polycystic ovaries on ultrasound and genetic heterogeneity. It was well-accepted that many lncRNAs and mRNAs were associated with PCOS, however, remain unclear. Therefore, the purpose of our study was to examine different expression profiles of lncRNAs and mRNAs in ovarian granulosa cells (GCs) in PCOS and Controls, and identify the correlation between lncRNAs, mRNAs and clinical parameters. Sixty five PCOS patients and 65 Controls were enrolled in this study and adopted standard long agonist protocols or GnRH antagonist protocols. Then 6 GCs samples in each group were subjected to high-thoughput sequencing and the remaining samples were used for the further verification by quantitative real-time PCR (qRT-PCR). Gene Oncology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) enrichment analysis were performed. We predicted the relationship between lncRNAs and mRNAs by Cytoscape software. According to the expression level of lncRNAs, mRNAs and the clinical parameters, we also explored their relationship and evaluate their predictive values for embryos quality and PCOS. We identified 1,049 differential expressed lncRNAs and 3,246 mRNAs (fold-change ≥2, p-value < 0.05). Seven lncRNAs (NONHSAT101926.2, NONHSAT136825.2, NONHSAT227177.1, NONHSAT010538.2, NONHSAT191377.1, NONHSAT230904.1, ENST00000607307) and 3 mRNAs (EREG, ENTPD6, YAP1) were validated consistent with sequence profile. Seven lncRNAs were related to hormone level and follicle counts, 3 mRNAs had connections with lipid metabolism. The area under curve (AUC) of 7 lncRNAs were valuable in distinguishing patients with PCOS from Controls. The AUC of NONHSAT230904.1 and NONHSAT227177.1 were 0.6807 and 0.6410, respectively, for distinguishing whether the rate of high-quality embryos exceeds 50%. Our study showed that the GCs lncRNAs and mRNAs were involved in the occurrence and development of PCOS, which contribute to clarify the pathogenesis mechanism of PCOS.

Melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS

Mitochondrial injury in granulosa cells (GCs) is associated with the pathophysiological mechanism of polycystic ovary syndrome (PCOS). Melatonin reduces the mitochondrial injury by enhancing SIRT1 (NAD-dependent deacetylase sirtuin-1), while the mechanism remains unclear. Mitochondrial membrane potential is a universal selective indicator of mitochondrial function. In this study, mitochondrial swelling and membrane defect mitochondria in granulosa cells were observed from PCOS patients and DHT-induced PCOS-like mice, and the cytochrome C level in the cytoplasm and the expression of BAX (BCL2-associated X protein) in mitochondria were significantly increased in GCs, with p-Akt decreased, showing mitochondrial membrane was damaged in GCs of PCOS. Melatonin treatment decreased mitochondrial permeability transition pore (mPTP) opening and increased the JC-1 (5,5′,6,6′-tetrachloro1,1′,3,3′-tetramethylbenzimidazolylcarbocyanine iodide) aggregate/monomer ratio in the live KGN cells treated with DHT, indicating melatonin mediates mPTP to increase mitochondrial membrane potential. Furthermore, we found melatonin decreased the levels of cytochrome C and BAX in DHT-induced PCOS mice. PDK1/Akt played an essential role in improving the mitochondrial membrane function, and melatonin treatment increased p-PDK 1 and p-Akt in vivo and in vitro. The SIRT1 was also increased with melatonin treatment, while knocking down SIRT1 mRNA inhibiting the protective effect of melatonin to activate PDK1/Akt. In conclusion, melatonin enhances SIRT1 to ameliorate mitochondrial membrane damage by activating PDK1/Akt in granulosa cells of PCOS.

Identification of the similarly expressed genes in patients with polycystic ovary syndrome and transsexuals.

Polycystic ovary syndrome (PCOS) is a common female infertility, which may be caused by excessive androgen, but its mechanism remains unknown. Transsexuals are women who take androgen drugs for a long time, and gradually have male signs. Their ovaries may have received high concentrations of androgen, which leads to the failure of ovarian reproductive function. Therefore, we searched the relevant data of PCOS and transsexuals in gene expression omnibus database, used limma package to identify the most similarly genes, and then analyzed the possible mechanism of PCOS through gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analysis. Then, the protein-protein interaction network was constructed by searching the String database, and the top 5 hub genes were identified by the cytohubba plug-in of Cytoscape. Finally, ubiquitin conjugating enzyme E2 E1 (UBE2E1), ubiquitin C (UBC), transcription elongation factor B subunit 1 (TCEB1), ubiquitin conjugating enzyme E2 N (UBE2N), and ring finger protein 7 (RNF7) genes were identified as the most similarly expressed genes between PCOS and Transsexuals. They may cause the ubiquitination of androgen receptor and eventually lead to sinus follicular growth arrest. In conclusion, 5 Central genes were identified in PCOS and transsexuals. These genes can be used as targets for early diagnosis or treatment of PCOS.

Markers of gastrointestinal permeability and dysbiosis in premenopausal women with PCOS: a case–control study

ObjectivesAltered intestinal permeability and gut barrier dysfunction have been suggested to play a role in the pathogenetic mechanism of polycystic ovary syndrome (PCOS), the most common endocrine and metabolic condition...

The role of FDX1 in granulosa cell of Polycystic ovary syndrome (PCOS)

BackgroundTo explore the development mechanism of PCOS and Transcriptomics was applied to seek the key gene.MethodsTranscriptomics marked by UID (unique identifier) technique of granulosa cell in PCOS and control women was carried out and key gene was picked up. Then the key gene in granulosa cell was measured by RT-PCR. Two PCOS models modeling with Letrozole and Testosterone Propionate were implemented and the key gene in granulosa cell of ovary was measured by immunohistochemistry to verify the relation with PCOS.ResultsGO-enrich of transcriptomics concentrated in domain steroid metabolism and domain mitochondria. Different genes were sought from coexisting in both domain steroid metabolism and domain mitochondria. Finally, five different genes including CYP11A1、CYB5R1、STAR、FDX1 and AMACR were obtained. RT-PCR was implemented to furtherly verify the downregulating mRNA of FDX1 in PCOS, which showed the consistent outcome with the transcriptomics. Level of FDX1 protein in granulosa cell of antral follicle in two PCOS models was measured and decreased.ConclusionsFDX1 was related with steroid metabolism and mitochondrial and may participate in the development of PCOS.

Disturbed Gastrointestinal Contractility in a Polycystic Ovary Syndrome Rat Model.

Polycystic ovary syndrome (PCOS), a common hormonal disorder in women, affects 4-18% of women of reproductive age worldwide. A higher prevalence of irritable bowel syndrome was found in women with PCOS. However, the effects and mechanism of PCOS on stomach and colon contractility remain unclear. This study aims to evaluate the correlation between PCOS and gastrointestinal disorder. Four-week-old female rats were subcutaneously implanted with pellets containing 7.5mg of dihydrotestosterone for 13weeks to create PCOS rat models. After vaginal smears, the estrus cycle stage was evaluated. Oral glucose tolerance test was performed after 90days of treatment. All animals were killed at 17weeks. The rats were fasted overnight and then anesthetized before decapitation, and the stomach fundus and colon were surgically removed and cultured in oxygenated Krebs solution. Acetylcholine and carbachol were used to evaluate the cholinergic system on contractility. The basal and stomach fundus responded with a reduced frequency and contractility in response to acetylcholine in the PCOS group. Moreover, no difference was found in the spontaneous stomach contractility induced by carbachol in both groups. Lower maximal colon muscle contractility was also found in response to acetylcholine stimulation in PCOS rats. Furthermore, lower maximal muscle contractility was found in response to extracellular calcium levels. MLC20 phosphorylation was also reduced in the gastrointestinal tissue in PCOS rats. PCOS induces gastroparesis and reduces gastrointestinal muscle contractility. This effect is, at least partly, through reducing the responsiveness of acetylcholine and MLC20 phosphorylation.

Serum metabolomics reveals metabolic profiling for women with hyperandrogenism and insulin resistance in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder. Hyperandrogenism (HA) and insulin resistance (IR) are two important pathogenic factors. We aimed to investigate the inherent disturbed metabolic profiles for women with HA or IR in PCOS as well as discover diagnostic biomarkers. A total of 286 subjects were recruited for the study. They constituted the following groups: healthy women (C), those with HA (B1), those with IR but not obese (B2) and obese women with IR (B3) in PCOS. Nine cross-comparisons with PCOS were performed to characterize metabolic disturbances. Serum metabolomic profiles were determined by gas chromatography-mass spectrometry. We found a total of 59 differential metabolites. 28 metabolites for B1 vs C, 32 for B2 vs C and 25 for B3 vs C were discovered. Among them, palmitic acid, cholesterol, myo-inositol, D-allose, 1,5-anhydro-D-sorbitol, 1-monopalmitin, 1-monostearin, glycerol 1-phosphate, malic acid and citric acid, were the common differential metabolites among B1 vs C, B2 vs C and B3 vs C, which related to biosynthesis of unsaturated fatty acids, citrate cycle etc. Besides, 9-biomarker panel can diagnose well between HA and IR in PCOS. They provided areas under the receiver operating characteristic curve of 0.8511 to 1.000 in the discovery phase, and predictive values of 90% to 92% in the validation set. The result indicated that the differential metabolites can reflect the underlying mechanism of PCOS and serve as biomarkers for complementary diagnosis of HA and IR in PCOS.

Inositols' Importance in the Improvement of the Endocrine-Metabolic Profile in PCOS.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility and metabolic problems among women of reproductive age. The mechanism of PCOS is associated with concurrent alterations at the hormonal level. The diagnosis assumes the occurrence of three interrelated symptoms of varying severity, namely ovulation disorders, androgen excess, or polycystic ovarian morphology (PCOM), which all require a proper therapeutic approach. The main symptom seems to be an increased androgen concentration, which in turn may contribute to different metabolic disorders. A number of papers have demonstrated the significant role of inositol therapy in PCOS. However, there is a lack of detailed discussion about the importance of myo-inositol (MI) and d-chiro-inositol (DCI) in reference to particular symptoms. Thus, the aim of this review is to present the effectiveness of MI and DCI treatment for PCOS symptoms. Moreover, the review is focused on analyzing the use of inositols, taking into account their physiological properties, together with the mechanism of individual PCOS symptom formation.

The phytoestrogen, quercetin, in serum, uterus and ovary as a potential treatment for dehydroepiandrosterone-induced polycystic ovary syndrome in the rat.

The exact mechanisms of polycystic ovary syndrome (PCOS) are unknown and there is no effective cure for the disease. The aim of this study was to evaluate the alterations in serum oestradiol and adiponectin levels and in the expression of some important genes in the uterine and ovarian tissues of PCOS rats. The therapeutic effect of quercetin on PCOS was also assessed. Rats were divided into five groups: control, ethanol, quercetin (Q), PCOS and PCOS+Q. After 30 days of oral treatments, the rats' ovaries and uteri were removed and nesfatin-1, aromatase and adipoR1 expressions were quantified with real-time polymerase chain reaction. Serum adiponectin and oestradiol levels were evaluated using enzyme-linked immunosorbent assay technique. The results of this study showed that expression of nesfatin-1 and adipoR1 genes and adiponectin serum levels decreased in the PCOS rats, but aromatase expression and oestradiol level increased. Treatment with quercetin increased the adiponectin level and expression of adipoR1 and nesfatin-1 and decreased both the expression of aromatase and the oestradiol level. Quercetin improved PCOS by phytoestrogenic effects and mimicking oestrogen's function. Quercetin also affects important factors in both the uterus and ovary and could improve the obesity and the diabetic and infertility symptoms of PCOS.