Progression Of Polycystic Ovary Syndrome Research Articles

Exploring the molecular mechanisms by which per- and polyfluoroalkyl substances induce polycystic ovary syndrome through in silico toxicogenomic data mining

The pathogeny of polycystic ovary syndrome (PCOS) is intricate, with endocrine disruptors (EDCs) being acknowledged as significant environmental factors. Research has shown a link between exposure to per- and polyfluoroalkyl substances (PFAS) and the development and progression of PCOS, although the precise mechanism is not fully understood. This study utilized toxicogenomics and comparative toxicogenomics databases to analyze data and investigate how PFAS mixtures may contribute to the development of PCOS. The results indicated that 74 genes are associated with both PFAS exposure and PCOS progression. Enrichment analysis suggested that cell cycle regulation and steroid hormone synthesis may be crucial pathways through which PFAS mixtures participate in the development of PCOS, involving important genes such as CCNB1 and SRD5A1. Furthermore, the study identified transcription factors (TFs) and miRNAs that may be involved in the onset and progression of PCOS, constructing regulatory networks encompassing TFs-mRNA interactions and miRNA-mRNA relationships to elucidate their regulatory roles in gene expression. By utilizing data mining techniques based on toxicogenomic databases, this study provides relatively comprehensive insights into the association between exposure factors and diseases compared to traditional toxicology studies. These findings offer new perspectives for further in vivo or in vitro investigations and contribute to understanding the pathogenesis of PCOS, thereby providing valuable references for identifying clinical treatment targets.

RNA-seq and miRNA-seq profiling analyses reveal molecular mechanisms underlying the progression of polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age, mainly characterized by menstrual disorders, infertility, and other symptoms. Due to its complex and multifactorial nature, the pathogenesis of PCOS remains unclear. MicroRNAs (miRNA) play vital roles in regulating gene expression. In this study, twelve ovarian granulosa cell samples from six PCOS patients and six non-PCOS women were collected as research objects. We aimed to identify key genes and miRNAs involved in the progression of PCOS using RNA-seq and small RNA-seq techniques, and to construct the corresponding miRNA-mRNA regulatory network. A total of 1552 differentially expressed genes (DEGs) and 52 differentially expressed (DE)-miRNAs were detected. Functional enrichment analyses suggested that the occurrence and development of PCOS might be closely related to processes such as glucose metabolism, hormone synthesis and cell function. The miRNA-mRNA regulatory network indicated that hsa-miR-330-5p and hsa-miR-663b may be candidate miRNAs that affect the development of PCOS. This study provides new clues for the pathogenesis of PCOS and a theoretical basis for new therapeutic targets.

Jujuboside A Attenuates Polycystic Ovary Syndrome Based on Estrogen Metabolism Through Activating AhR-mediated CYP1A2 Expression.

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women. This study aimed to investigate the therapeutic effects and mechanism of Jujuboside A on PCOS using a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Estrogen and androgen homeostasis was evaluated in serum from both clinical samples and PCOS mice. The stages of the estrous cycle were determined based on vaginal cytology. The ovarian morphology was observed by stained with hematoxylin and eosin. Moreover, we analyzed protein expression of cytochrome P450 1A1 (CYP1A1), cytochrome P450 1A2 (CYP1A2) and aryl hydrocarbon receptor (AhR) in ovary and KGN cells. Molecular docking, immunofluorescence, and luciferase assay were performed to confirm the activation of AhR by Jujuboside A. Jujuboside A effectively alleviated the disturbance of estrogen homeostasis and restored ovarian function, leading to an improvement in the occurrence and progression of PCOS. Furthermore, the protective effect of JuA against PCOS was dependent on increased CYP1A2 levels regulated by AhR. Our findings suggest that Jujuboside A improves estrogen disorders and may be a potential therapeutic agent for the treatment of PCOS.

Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS.

Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)? Increased ovarian ferroptosis was present in PCOS ovaries and the inhibition of ferroptosis with ferrostatin-1 (Fer-1) ameliorated polycystic ovary morphology and anovulation. Programmed cell death plays a fundamental role in ovarian follicle development. However, the types and mechanisms of cell death involved in the ovary are yet to be elucidated. Ferroptosis is a recently discovered iron-dependent programmed cell death. Impaired iron metabolism and cell death have been observed in women with PCOS, the main cause of anovulatory infertility. Additionally, previous studies reported that an abnormal expression of noncoding RNA may promote ferroptosis in immortalized ovarian granulosa cell lines. However, little is known about whether ovarian ferroptosis is increased in PCOS, and there is insufficient direct evidence for a role of ferroptosis in PCOS, and the underlying mechanism. Moreover, the effect of the inhibition of ferroptosis with Fer-1 in PCOS remains unclear. Ferroptosis was evaluated in human granulosa cells (hGCs) from non-PCOS (n = 6-16) and PCOS (n = 7-18) patients. The experimental study was completed in vitro using primary hGCs from women undergoing IVF. Improvements in PCOS indicators following ferroptosis inhibition with Fer-1 were investigated in a dehydroepiandrosterone (DHEA)-induced PCOS rat model (n = 8 per group). Ovarian ferroptosis was evaluated in the following ways: by detecting iron concentrations via ELISA and fluorescent probes; measuring malondialdehyde (MDA) concentrations via ELISA; assessing ferroptosis-related protein abundance with western blotting; observing mitochondrial morphology with transmission electron microscopy; and determining cell viability. Primary hGCs were collected from women undergoing IVF. They were treated with dihydrotestosterone (DHT) for 24 h. The effect of DHT on ferroptosis was examined in the presence or absence of small interfering RNA-mediated knockdown of the putative receptor coregulator for signaling molecules. The role of ovarian ferroptosis in PCOS progression was explored in vivo in rats. The DHEA-induced PCOS rat model was treated with the ferroptosis inhibitor, Fer-1, and the oocytes and metaphase II oocytes were counted after ovarian stimulation. Additionally, rats were treated with the ferroptosis inducer, RSL3, to further explore the effect of ferroptosis. The concentrations of testosterone, FSH, and LH were assessed. Increased ferroptosis was detected in the ovaries of patients with PCOS and in rats with DHEA-induced PCOS. Increased concentrations of Fe2+ (P < 0.05) and MDA (P < 0.05), and upregulated nuclear receptor coactivator 4 protein levels, and downregulated ferritin heavy chain 1 (FTH1) and glutathione peroxidase 4 (GPX4) proteins were observed in the hGCs in patients with PCOS and ovaries of PCOS rats (P < 0.05 versus control). DHT was shown to induce ferroptosis via activation of NOCA4-dependent ferritinophagy. The inhibition of ferroptosis with Fer-1 in rats ameliorated a cluster of PCOS traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, polycystic ovaries, anovulation, and oocyte quality (P < 0.05). Treating rats with RSL3 resulted in polycystic ovaries and hyperandrogenism (P < 0.05). N/A. Although ovarian-targeted ferroptosis inhibition may be a more targeted treatment for PCOS, the underlying mechanisms in the cycle between ferroptosis and hyperandrogenism require further exploration. Additionally, since PCOS shows high heterogeneity, it is important to investigate whether ferroptosis increases are present in all patients with PCOS. Androgen-induced ovarian ferroptosis appears to play a role in the pathogenesis of PCOS, which potentially makes it a promising treatment target in PCOS. This study was supported by the National Key R&D Program of China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), National Natural Science Foundation of China (No. 82130046, 82320108009, 82101708, 82101747, and 82001517), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (No. SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003) and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (No. 20161413), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors report no competing interests.

Analysis of Genetic Spectrum in Polycystic Ovary Syndrome- A Review

Polycystic ovary syndrome (PCOS) is increase in an alarming rate since 1935. According to WHO the prevalence rate of PCOS is 3.4% worldwide. Hyperandrogenism, chronic anovulation, small cysts and increase in size of the ovary are the most common diagnostic feature for PCOS. Beside the environmental factors PCOS is highly associated with genetic back up of an individual. So, Different genetic pathways like steroid hormone synthesis , ovarian and adrenal steroidogenesis, gonadotropin action, insulin action and secretion, energy homeostasis , chronic inflammation pathways plays most important role in PCOS progression. Furthermore several report suggested that, some other genes like plasminogen activator inhibitor-1 (PAI-1), HSD3B2 , 17α-hydroxysteroid dehydrogenases, dopamine receptor, IGF107, aldosterone synthetase , paraoxonase, glycogen synthetase, resistin, apoprotein E are also involved in PCOS progression. From different case report it is established that epilepsy and diabetes condition are the two main regulators for PCOS progression. Whereas, epigenetic mechanism is also involved in the pathogenesis of PCOS. Some of the therapeutics is also available for treatment of PCOS but not ensure proper cure. Long-term treatment for PCOS, increases the risk of developing metabolic and cardiovascular abnormalities. So the main aim of this review is to reveal all aspects of genetics mechanism related to PCOS for better understanding of the disease. As well as established a profile of regulatory marker gene for early diagnosis and to develop a better treatment protocol.

Deconvolution at the single-cell level reveals ovarian cell-type-specific transcriptomic changes in PCOS

BackgroundPolycystic ovary syndrome (PCOS) is one of the most common reproductive endocrine disorders in females of childbearing age. Various types of ovarian cells work together to maintain normal reproductive function, whose discordance often takes part in the development and progression of PCOS. Understanding the cellular heterogeneity and compositions of ovarian cells would provide insight into PCOS pathogenesis, but are, however, not well understood. Transcriptomic characterization of cells isolated from PCOS cases have been assessed using bulk RNA-seq but cells isolated contain a mixture of many ovarian cell types.MethodsHere we utilized the reference scRNA-seq data from human adult ovaries to deconvolute and estimate cell proportions and dysfunction of ovarian cells in PCOS, by integrating various granulosa cells(GCs) transcriptomic data.ResultsWe successfully defined 22 distinct cell clusters of human ovarian cells. Then after transcriptome integration, we obtained a gene expression matrix with 13,904 genes within 30 samples (15 control vs. 15 PCOS). Subsequent deconvolution analysis revealed decreased proportion of small antral GCs and increased proportion of KRT8high mural GCs, HTRA1high cumulus cells in PCOS, especially increased differentiation from small antral GCs to KRT8high mural GCs. For theca cells, the abundance of internal theca cells (TCs) and external TCs was both increased. Less TCF21high stroma cells (SCs) and more STARhigh SCs were observed. The proportions of NK cells and monocytes were decreased, and T cells occupied more in PCOS and communicated stronger with inTCs and exTCs. In the end, we predicted the candidate drugs which could be used to correct the proportion of ovarian cells in patients with PCOS.ConclusionsTaken together, this study provides insights into the molecular alterations and cellular compositions in PCOS ovarian tissue. The findings might contribute to our understanding of PCOS pathophysiology and offer resource for PCOS basic research.

Susceptibility loci identified in Han Chinese influence genetic predisposition of PCOS in Indian women.

Polycystic ovary syndrome (PCOS) is a multifactorial disorder characterized by a broad spectrum of reproductive and metabolic perturbations, necessitating early timely diagnosis and management. PCOS is a multigenic disorder and ample evidence from family based, candidate gene and genome-wide association studies (GWAS) has implicated genetic factors in development and progression of PCOS. The first GWASs in Han Chinese population revealed prominent gene loci to be strong contenders in the etiopathogenesis of PCOS. However, different ethnic and geographical settings impact the genetic association pattern of PCOS. In the current case-control replication study, we have genotyped previously identified polymorphisms viz. rs2479106 and rs10818854 of DENND1A and rs13405728 of LHCGR, rs4385527 and rs3802457 of c9orf3, rs705702 of RAB5B and rs1894116 of YAP1 in control (N = 247) and PCOS (N = 504) women by Sanger sequencing, and their association with PCOS susceptibility and its related traits was investigated. We found significant association of rs4385527 of c9orf3 and rs1894116 of YAP1 with decreased and increased PCOS susceptibility respectively in non-hyperandrogenic women. Trend towards association was also noted for rs2479106 of DENND1A and rs705702 of RAB5B. Additionally, polymorphisms also showed association with metabolic and androgen related traits in both controls and hyper- and non-hyperandrogenic women with PCOS. Thus, this study shows that some, but not all polymorphisms previously identified in Han Chinese women, could contribute to the genetic pathophysiology of PCOS in Indian women, accentuating essentiality of conducting replication studies to elucidate the genetic predisposition profile of PCOS.

Programmed cell death 4: A novel player in the pathogenesis of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a pathological condition recognized by menstrual cycle irregularities, androgen excess, and polycystic ovarian morphology, affecting a significant proportion of women of childbearing age and accounting for the most prevalent cause of anovulatory sterility. In addition, PCOS is frequently accompanied by metabolic and endocrine disturbances such as obesity, dyslipidemia, insulin resistance, and hyperinsulinemia, indicating the multiplicity of mechanisms implicated in the progression of PCOS. However, the exact pathogenesis of PCOS is yet to be elucidated. Programmed cell death 4 (PDCD4) is a ubiquitously expressed protein that contributes to the regulation of various cellular processes, including gene expression, cell cycle progression, proliferation, and apoptosis. Despite some disparities concerning its exact cellular effects, PDCD4 is generally characterized as a protein that inhibits cell cycle progression and proliferation and instead drives the cell into apoptosis. The apoptosis of granulosa cells (GCs) is speculated to take a major part in the occurrence and progression of PCOS by ceasing antral follicle development and compromising oocyte competence. Given the possible involvement of GC apoptosis in the progression of PCOS, as well as the contribution of PDCD4 to the regulation of cell apoptosis and the development of metabolic diseases, the current review aimed to discuss whether or how PDCD4 can play a role in the pathogenesis of PCOS by affecting GC apoptosis.

An Overview: Polycystic Ovary Syndrome and Related Future Methods

Polycystic ovary syndrome (PCOS) is a common hormonal disorder that affects females with ovaries, typically during their reproductive years. Many signs are present, such as irregular menstrual periods, elevated levels of androgen (male hormone), and the development of cysts—small, fluid-filled sacs—on the ovaries. Its symptoms progress from minor to severe, such as the first signs of hirsutism and acne, which worsen and cause irregular menstruation and infertility. Insulin resistance, weight gain, infertility, and a higher risk of type 2 diabetes and cardiovascular disease are just a few of the health issues that PCOS can cause. While the precise etiology of PCOS remains unclear, a hereditary and environmental combination is thought to be involved. Numerous diagnostic instruments are available, including blood testing for insulin resistance and ultrasonography. Depending on the patient's needs, therapy options for PCOS may include Ayurveda medicine, hormone medication, lifestyle modifications, and fertility therapies. PCOS treatment options typically center on treating symptoms. The long-term health risks associated with PCOS must be reduced by early diagnosis and appropriate management. There are various forms of future perception, including Determining the factors that contribute to the onset and progression of PCOS after birth and clarifying the underlying mechanisms, clarifying the processes that underlie PCOS's high heredity, finding biomarkers that might be utilized to identify those who are highly likely to have PCOS in their early years.

Polikistik Over Sendromlu (PKOS) Kadınlarda Anormal MiRNA Ekspresyonu

Polycystic ovary syndrome (PCOS) is a debilitating endocrine and metabolic disorder that affects a large proportion of women in their reproductive years. It differs by a range of symptoms including polycystic ovary appearance, hyperandrogenism, chronic anovulation, insulin resistance, and obesity. Despite years of research, the exact cause of PCOS remains elusive, but recent studies have suggested that epigenetic mechanisms may play a significant role in its pathogenesis. Of particular interest are micro-RNAs (miRNAs), short non-coding RNAs that are transcribed from DNA but not translated into protein. Recent research has demonstrated that abnormal expression of miRNAs is present in PCOS and may contribute to the development and progression of the disease. This review aims to provide an in-depth analysis of the current knowledge and challenges related to abnormal miRNA expression in PCOS, shedding light on a potential avenue for targeted therapies and improved management of this debilitating condition. The review summarizes the findings from various studies that have investigated the role of miRNAs in PCOS. It discusses the specific miRNAs that have been found to be dysregulated in PCOS and their potential impact on the pathophysiology of the disease. The review also highlights the challenges associated with studying miRNAs, including the complexity of their regulation and the need for standardized methodologies for miRNA profiling. Based on the available evidence, abnormal expression of miRNAs appears to be a significant contributor to the development and progression of PCOS. Targeting these dysregulated miRNAs could offer new therapeutic strategies for the management of PCOS. Biomarkers and gene therapies associated with miRNA may improve the accuracy and effectiveness of PCOS diagnosis and treatment. However, further research is needed to fully understand the functional roles of specific miRNAs and their potential as diagnostic or therapeutic targets.

The role of the thyroid in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disease in women of childbearing age and can cause metabolic disorder, infertility, and increased anxiety and depression; as a result, it can seriously affect the physical and mental health of fertile women. PCOS is a highly clinically heterogeneous disease with unclear etiology and pathogenesis, which increases the difficulty of treatment. The thyroid gland has complex regulatory effects on metabolism, reproduction, and emotion, and produces hormones that act on almost all cells of the human body. The clinical manifestations of PCOS are similar to some thyroid diseases. Furthermore, some thyroid diseases, such as subclinical hypothyroidism (SCH), not only increase the incidence rate of PCOS, but also exacerbate its associated metabolic abnormalities and reproductive disorders. Interestingly, PCOS also increases the incidence of some thyroid diseases. However, the role of the thyroid in PCOS remains unclear. This review is intended to thoroughly explore the critical role of the thyroid in PCOS by summarizing the comorbidity of PCOS and thyroid diseases and their combined role in metabolic disorders, related metabolic diseases, and reproductive disorders; and by analyzing the potential mechanism through which the thyroid influences the development and progression of PCOS and its symptoms. We hope this review will provide a valuable reference for the role of the thyroid in PCOS.

A novel model based on necroptosis to assess progression for polycystic ovary syndrome and identification of potential therapeutic drugs.

Polycystic ovary syndrome (PCOS), a common endocrine and reproductive disorder, lacks precise diagnostic strategies. Necroptosis was found to be crucial in reproductive and endocrine disorders, but its function in PCOS remains unclear. We aimed to identify differentially diagnostic genes for necroptosis (NDDGs), construct a diagnostic model to assess the progression of PCOS and explore the potential therapeutic drugs. Gene expression datasets were combined with weighted gene co-expression network analysis (WGCNA) and necroptosis gene sets to screen the differentially expressed genes for PCOS. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to construct a necroptosis-related gene signatures. Independent risk analyses were performed using nomograms. Pathway enrichment of NDDGs was conducted with the GeneMANIA database and gene set enrichment analysis (GSEA). Immune microenvironment analysis was estimated based on ssGSEA algorithm analysis. The Comparative Toxicogenomics Database (CTD) was used to explore potential therapeutic drugs for NDDGs. The expression of NDDGs was validated in GSE84958, mouse model and clinical samples. Four necroptosis-related signature genes, IL33, TNFSF10, BCL2 and PYGM, were identified to define necroptosis for PCOS. The areas under curve (AUC) of receiver operating characteristic curve (ROC) for training set and validation in diagnostic risk model were 0.940 and 0.788, respectively. Enrichment analysis showed that NDDGs were enriched in immune-related signaling pathways such as B cells, T cells, and natural killer cells. Immune microenvironment analysis revealed that NDDGs were significantly correlated with 13 markedly different immune cells. A nomogram was constructed based on features that would benefit patients clinically. Several compounds, such as resveratrol, tretinoin, quercetin, curcumin, etc., were mined as therapeutic drugs for PCOS. The expression of the NDDGs in the validated set, animal model and clinical samples was consistent with the results of the training sets. In this study, 4 NDDGs were identified to be highly effective in assessing the progression and prognosis of PCOS and exploring potential targets for PCOS treatment.

Probiotics and Polycystic Ovary Syndrome: A Perspective for Management in Adolescents with Obesity.

Polycystic ovary syndrome (PCOS) affects a considerable percentage of females of reproductive age. PCOS is an obesity-related condition and its effects are greatly amplified by obesity. Even though the pathogenesis of PCOS remains complex and has not been fully elucidated, a link between obesity, PCOS, and dysbiosis has been described. The potential role of the gut microbiota in the development and progression of PCOS and its associated symptoms has also been reported. The aim of this narrative review is to present a non-systematic analysis of the available literature on the topic of probiotics and PCOS in adolescents with obesity in order to revise the beneficial effects of probiotics/symbiotic supplementation on hormonal and metabolic profiles and inflammatory conditions. The effectiveness of probiotics/synbiotics in PCOS has been supported. The literature suggests that probiotic/symbiotic supplementation may ameliorate hormonal profiles, inflammatory indicators, and lipid metabolism disturbances caused by PCOS. Studies also show improvements in weight, BMI, insulin, and HOMA-IR, including a potential role it plays in protecting fertility. Even though further studies are needed to confirm these findings, particularly in adolescent patients, probiotic supplementation may be considered a solution for managing PCOS in adolescents with obesity.

Circular RNA as a Novel Regulator and Promising Biomarker in Polycystic Ovary Syndrome.

Polycystic ovary syndrome (PCOS) is a prevalent metabolic and reproductive disorder that causes low fertility in females. Despite its detrimental effects on women's health, care for PCOS has been impeded by its undefined pathogenesis. Thus, there is an urgent need to explore novel biomarkers and therapeutic targets for the diagnosis and treatment of PCOS. Circular RNAs (circRNAs) are a class of noncoding RNAs with covalently closed cyclic structures, present in high abundance, and show development-stage specific expression patterns. Recent studies have demonstrated that circRNAs participate in PCOS progression by modulating various biological functions, including cell proliferation, apoptosis, and steroidogenesis. In addition, circRNAs are widely present in the follicular fluid of women with PCOS, indicating their potential as diagnostic biomarkers and therapeutic targets for PCOS. This review provides the current knowledge of circRNAs in PCOS, including their regulatory functions and molecular mechanisms, and explores their potential as diagnostic biomarkers and therapeutic targets.

The Role of Circadian Rhythms in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS), as a most common metabolic disrupted disease, has several main symptoms, including ovarian insufficiency, hyperandrogenism, insulin resistance, etc., which may lead to female infertility. Many studies on the processes of PCOS have been done throughout the years, but unfortunately, the pathophysiology of PCOS is still not fully figured out. The circadian rhythm is the metronomic adjustment of the organisms to the external environment at all levels, from the molecular to the individual. It is revealed in multiple studies that there is a clear association between the progression of PCOS and the disturbance of circadian rhythms. Numerous studies have demonstrated that circadian rhythms can influence the development of PCOS by altering the Wnt/β-catenin, GPCR/cAMP/PKA, PI3K/AKT, and MAPK signaling pathways of the hypothalamic-pituitary-ovarian/hypothalamic-pituitary-adrenal axis, which result in abnormal hormone expression, receptor resistance, and metabolic disorders. The circadian rhythm misalignment may contribute to the formation and development of PCOS through the expression of certain genes that control the canonical signaling pathway. It is foreseeable that more preventive and targeted treatment for PCOS is the hot zone of clinical research in the future. This article aimed to review the state regarding the link between circadian rhythm disorder and PCOS, focus on the pathophysiology of PCOS, explore the pathways of circadian rhythm in the process of PCOS, and seek to offer a clear direction and practical approach for the prevention and treatment of PCOS.

LncRNA PWRN2 promotes polycystic ovary syndrome progression via epigenetically reducing ATRX by recruiting LSD1

Long non-coding RNA has been shown to mediate the progression of polycystic ovary syndrome (PCOS). However, the role and mechanism of Prader-Willi region nonprotein coding RNA 2 (PWRN2) in PCOS progression remain unclear. In our study, Sprague-Dawley rat was injected with dehydroepiandrosterone to mimic PCOS rat models. HE staining was used to assess the number of benign granular cells, and serum insulin and hormone levels were detected by ELISA kit. The expression of PWRN2 was examined by qRT-PCR. Ovarian granulosa cells (GCs) proliferation and apoptosis were examined by CCK-8 assay and flow cytometry. The protein levels of apoptosis markers and Alpha thalassemia retardation syndrome X-linked (ATRX) were determined by western blot. The interaction between lysine-specific demethylase 1 (LSD1) and PWRN2 or ATRX was confirmed by RIP and ChIP assay. Our data showed that PWRN2 was upregulated and ATRX was downregulated in the ovarium tissues and serum of PCOS rat. PWRN2 knockdown promoted GCs proliferation and inhibited apoptosis. In the mechanism, PWRN2 inhibited ATRX transcription by binding with LSD1. In addition, downregulation of ATRX also eliminated the effect of sh-PWRN2 on GCs growth. In conclusion, our data suggested that PWRN2 might restrain GCs growth to promote PCOS progression, which was achieved by binding with LSD1 to inhibit ATRX transcription.

Chao Nang Qing prescription promotes granulosa cell apoptosis and autophagy by targeting GATA3

Objective Polycystic ovary syndrome (PCOS) is a common endocrine disease in women of reproductive age, with complex pathological symptoms and mechanisms. This study explored the mechanism of action of Chao Nang Qing prescription (CNQP) in PCOS. Methods CNQP-medicated serum was prepared for culturing KGN granulosa cells. GATA3 knockdown, MYCT1 overexpression, and MYCT1 knockdown vectors were constructed to transfect KGN cells. Cell proliferation and apoptosis, as well as the expression of autophagy-related LC3-II/I, Beclin-1, and p62, were analyzed. ChIP was used to detect the binding of GATA3 and the MYCT1 promoter, and dual-luciferase reporter assay was used to analyze the influence of GATA3 on MYCT1 promoter activity. Results CNQP treatment reduced proliferation, increased apoptosis, elevated LC3-II/I, Beclin-1, GATA3, and MYCT1 expression, and decreased p62 expression in KGN cells. GATA3 bound to the MYCT1 promoter to promote MYCT1 expression. MYCT1 overexpression impeded proliferation and stimulated apoptosis and autophagy in KGN cells. Compared to CNQP treatment alone, GATA3 or MYCT1 knockdown before CNQP treatment promoted proliferation and reduced apoptosis and autophagy in KGN cells. Conclusion CNQP may modulate KGN cell activity by upregulating GATA3 and MYCT1 expression, thereby slowing down the progression of PCOS.

Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis

Context Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS. Objective This study determines whether baicalin could affect the progression of PCOS. Materials and methods To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 μM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 μM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect. Conclusions Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

Assessment Between Follicular Fluid Multiple Element Concentrations and Hormonal Profiles of Women with Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive-aged women. Follicular fluid quality affects early embryonic development and multiple stages of pregnancy. This study measured 12 elements in follicular fluid and 5 blood hormones, aiming to identify the associations between multielement concentrations, as well as blood hormone levels, and PCOS to investigate the interference of multielement coexposure on PCOS and examine the potential roles of hormones. Eight elements (As, Cu, Se, Sr, V, Zn, Cr, Ca), but not Mg, showed a positive dose–effect relationship with PCOS. The OPLS models of follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) with relevant elements showed that Mg, Zn, Fe, Se, and V had a more significant effect on FSH and that As, Se, V, Cu, and Zn were positively correlated with AMH (VIP > 1). Further analysis indicated a synergistic effect for FSH and Mg, both of which were protective factors against PCOS; the associations between the five elements and PCOS incidence were mediated by AMH. Changes in hormone levels between multielement coexposure and PCOS development suggest that FSH and Mg are protective against PCOS; female exposure to As, Se, V, Cu, and Zn may affect PCOS progression by perturbing AMH levels.

Insights on the NF-κB system in polycystic ovary syndrome, attractive therapeutic targets.

The nuclear factor κappa B (NF-κB) signaling plays a well-known function in inflammation and regulates a wide variety of biological processes. Low-grade chronic inflammation is gradually considered to be closely related to the pathogenesis of Polycystic ovary syndrome (PCOS). In this review, we provide an overview on the involvement of NF-κB in the progression of PCOS particularly, such as hyperandrogenemia, insulin resistance, cardiovascular diseases, and endometrial dysfunction. From a clinical perspective, progressive recognition of NF-κB pathway provides opportunities for therapeutic interventions aimed at inhibiting pathway-specific mechanisms. With the accumulation of basic experimental and clinical data, NF-κB signaling pathway was recognized as a therapeutic target. Although there have been no specific small molecule NF-κB inhibitors in PCOS, a plethora of natural and synthetic compound have emerged for the pharmacologic intervention of the pathway. The traditional herbs developed for NF-κB pathway have become increasingly popular in recent years. Abundant evidence elucidated that NF-κB inhibitors can significantly improve the symptoms of PCOS. Herein, we summarized evidence relating to how NF-κB pathway is involved in the development and progression of PCOS. Furthermore, we present an in-depth overview of NF-κB inhibitors for therapy interventions of PCOS. Taken together, the NF-κB signaling may be a futuristic treatment strategy for PCOS.