Causes Of Polycystic Ovary Syndrome Research Articles

Effect of Rhei Radix Et Rhizome on treatment of polycystic ovary syndrome by regulating PI3K/AKT pathway and targeting EGFR/ALB in rats

Ethnopharmacological relevanceAbnormal endocrine metabolism caused by polycystic ovary syndrome (PCOS) poses a serious risk to reproductive health in females. According to Traditional Chinese Medicine (TCM) theories, the leading causes of PCOS include turbid phlegm, blood stasis and stagnation of liver Qi. Rhei Radix Et Rhizome is widely used in TCM to attack stagnation, clear damp heat, relieve fire. Rhei Radix Et Rhizome is an important part of the TCM formulas for the treatment of PCOS, which has a long history of medicinal use. However, the specific effect and mechanisms of Rhei Radix Et Rhizome on PCOS have yet to be elucidated. Aim of the studyThe object of this study aimed to investigate the effect and its pharmacological mechanism of Rhei Radix Et Rhizome on the treatment of polycystic ovary syndrome. MethodsPCOS was induced in female Sprague Dawley (SD) rats by administering letrozole (1 mg/kg, per orally, p.o.) for 21 days, then treated with Rhei Radix Et Rhizome at doses of 0.6 g/kg or 1.2 g/kg. Rats weight, blood glucose and estrus period are measured, and serum hormone include free testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH) and ovarian lesions were observed to determine the effects of Rhei Radix Et Rhizome. Network pharmacology and molecular docking predicted the targets of Rhei Radix Et Rhizome on PCOS. Epidermal growth factor receptor (EGFR), albumin (ALB), PI3K and P-AKT/AKT protein expression levels in ovarian tissues were assessed by Western blot. ResultsRhei Radix Et Rhizome reduce abnormal weight and fasting blood glucose induced by letrozole (n = 5, p < 0.01), and improve the disturbed estrus cycle, reduce T, LH levels and LH/FSH ratio of PCOS rats (n = 4, p < 0.01). In addition, it alleviates the polycystic changes of ovaries in PCOS rats and reduces ovarian histopathological damage (n = 4, p < 0.01). Additionally, the core active components of Rhei Radix Et Rhizome for PCOS include Sennoside D_qt, Procyanidin B-5,3′-O-gallate, and Mutatochrome, which strongly bind to core therapeutic targets ALB and EGFR. Furthermore, the treatment reduces the increase of EGFR and ALB induced by letrozole (n = 4, p < 0.01). KEGG pathway enrichment analysis highlights endocrine resistance and prolactin signaling pathway, in both of which the PI3K/AKT pathway plays a crucial role. Our results show Rhei Radix Et Rhizome rescue the abnormal expression of PI3K/AKT pathway in PCOS rats (n = 4, p < 0.01). However, no significant dose-dependent relationship was observed in the tested dose range for the above experiments. ConclusionThese findings suggest that Rhei Radix Et Rhizome can regulate the PI3K/AKT pathway and target EGFR and ALB to treat polycystic ovary syndrome in rats. This study provides a scientific basis for the use of Rhei Radix Et Rhizome in the treatment of PCOS and highlights its potential mechanism through modulation of the PI3K/AKT pathway.

Decreased Insulin and Interleukin-6 Levels in Rattus Norvegicus Model of Polycystic Ovary Syndrome-Insulin Resistance Treated with a High Protein Diet

Hypercaloric in women of childbearing age is one of the causes of polycystic ovary syndrome (PCOS) with insulin resistance. Increased inflammation (tumor factor necrosis-α (TNF-α) and interleukin-6 (IL-6)) is the impact of endocrine and metabolic disorders involved due to metabolic syndrome, obesity, and diabetes mellitus. This study aims to evaluate whether a high-protein diet can reduce insulin and interleukin-6 levels, which are key indicators of polycystic ovary syndrome, and whether these changes can help in the treatment of the syndrome. This study used a prepost test only control design, true experimental, with a total sample of 6 female Rattus norvegicus rats aged 2–3 years (150–200 g). It consists of 4 groups, namely the negative control group (K-), the positive control group (K+), the treatment group (P), and the group without treatment (P-). The study examined the rat blood serum ELISA measurement of insulin and IL-6 levels. Anova test results of IL-6 levels (p = 0.002). Post-hoc test results of group K- and group P (p = 0.002), group K + and group P (p = 0.037), group K- and group K + (p = 0.437). The Anova test results of insulin levels between groups found a significant difference (p = 0.001). Post-hoc test of insulin levels of group K- and group P (p = 0.002), group K- and group K+ (p = 0.000), and group K+ with group P (p = 0.356). In group K and group P, the results of the ANOVA and post hoc tests on IL-6 levels and insulin levels with the provision of a high-protein diet show significant differences. This study suggests that a high-protein diet may be an effective therapeutic alternative in reducing the symptoms of polycystic ovary syndrome, especially in controlling high insulin and interleukin-6 levels.

The Impact of Microparticulate Air Pollution in Polycystic Ovary Syndrome: A Narrative Review

Objective: The aim of this narrative review is to summarize studies examining the relationship between microparticulate air pollution (MAP) and polycystic ovary syndrome (PCOS). Mechanism: PCOS is increasingly regarded as an evolutionary mismatch disorder that manifests in women due to exposure to a range of lifestyle and environmental factors. Although the underlying causes of PCOS remain debated, environmental factors such as endocrine-disrupting chemicals (EDC), may contribute to its pathogenesis due to their well-documented hormonal and metabolic effects. MAP is another significant environmental exposure that has been associated with a variety of chronic diseases, as well as adverse hormonal and metabolic effects, including PCOS. Chronic low-grade inflammation and insulin resistance (IR) are key pathophysiological features of PCOS that have been associated with inhalation and ingestion of MAP. Findings in Brief: Our search identified four studies that systematically examined the relationship between MAP and PCOS. One population-based cohort study showed an increased risk of PCOS with increased exposure to various air pollutants, including MAP. A second population-based study showed a decreased risk of PCOS with increasing levels of exposure, while a longer duration of exposure was associated with an increased risk of PCOS. A third study found that conception rates were lower in women with PCOS exposed to second-hand smoke (SHS) compared to non-exposed women. In contrast, a fourth study reported that exposure to air pollutants was not associated with reduced pregnancy outcomes. These data suggest that both the concentration and duration of exposure to MAP may be important factors, and that reproductive outcomes could be affected by exposure to MAP through second-hand cigarette smoke. Conclusions: Preliminary data suggest that MAP may contribute to an increased risk of PCOS, although the available evidence remains inconsistent. Nevertheless, the current evidence supports advising women to avoid exposure to SHS and MAP whenever possible. This review highlights the need for further research on the effects of MAP in women with PCOS.

Investigation of the Effect of Nano-melatonin on Oxidative Stress in Sera of Patients with Polycystic Syndrome

Background: The association between polycystic ovary syndrome (PCOS) and oxidative stress in women, the possible causes of PCOS, insulin resistance (IR), obesity, and oxidative stress. Oxidants are chemical elements that tend to gain electrons, losing positive charge. The Oxidative Stress (OS) is defined as an imbalance between the formation and synthesis of free radicals and the antioxidant defense system, which results in oxidative damage. Objective: The purpose of this research is to investigate the effect of nano-melatonin on oxidative stress in the sera of patients with polycystic syndrome. Methods: The study includes 120 Iraqi women, divided into two groups: 60 PCOS patients and 60 healthy control patients. Sample Analysis Biochemistry analyses the hormonal profile and determines the hormonal levels (LH, FSH, Testosterone, and Prolactin) that were identified for all controls and patients. Hormones analysis was performed using the enzyme-linked fluorescent assay (ELFA) technique. Synthesized ML nanoparticles by ultrasonic sonication. Results: The results indicate that the mean of serum LH significantly increased (P&lt;0.02) in PCOS BMI ≥ 25 patients G1 (6.19±3.13) mIU/mL compared with controls C1 (4.504±1.591) mIU/mL, while a nonsignificant difference (P&gt;0.05) when compared the BMI&lt;25 kg/m2 for G2 (5.55±1.93) with control group C2 (6.31±2.58) of luteinizing hormone in G1 and G2. Conclusions: An increased ratio of LH to FSH was shown to be characteristic of PCOS. For PCOS, high LH values are crucial. For the purpose of diagnosing PCOS, high LH values are crucial release of gonadotropin hormones (LH, FSH) from the pituitary. To higher the production of androgen in ovarian theca cells, The LH receptor is activated by the luteinizing hormone (LH). The nano Mel was higher in the inhibition of Oxidative stress two causes nano-melatonin high surface area and small size.

The association of CYP11A1 gene polymorphisms with the polycystic ovary syndrome patients.

The objective of this study was to investigate the allele frequencies of polymorphisms in genes CYP11A1 rs4886595 and CYP11A1 rs4887139 that are responsible for the steroidogenesis mechanism in polycystic ovary syndrome patients and control females. Samples were obtained from the Department of Obstetrics and Gynecology in the Near East University Hospital from September 2019 to December 2019. Only the nonobese patients between the ages of 18-40 years were included in this study following informed consent. Obese patients and patients more than 40 years of age were excluded from the study. Nonobese women and normal ovulation were included in the control group. DNA was isolated from blood samples. Real-time polymerase chain reaction (PCR) was used to analyze single nucleotide polymorphisms (SNPs) in various genes linked to polycystic ovary syndrome. The studies were carried out using the samples obtained from 120 women, of whom 55 were nonobese and had normal ovulation, and 65 were polycystic ovary syndrome patients. The allelic frequencies of SNPs in genes linked to polycystic ovary syndrome were calculated using real-time PCR outcomes. The variation of the CYP11A1 rs4887139 G>A did not show any significance, while the variation of CYP11A1 rs4886595 C>A showed significant differences between the patient and the control groups (p=0.01), respectively. Future research ought to focus on elucidating the susceptible causes of polycystic ovary syndrome with a wide range of SNPs and more sample size. The genome-wide association studies in polycystic ovary syndrome patients of different origin will be important to identify candidate genes as well as proteins that are implied in polycystic ovary syndrome risk.

Whole Exome Sequencing Reveals Rare Variants in Genes Associated with Metabolic Disorders in Women with PCOS.

Polycystic ovary syndrome (PCOS) is a complex genetic trait, the pathogenesis of which is governed by an interplay of genetic and epigenetic factors. However, the aetiology of PCOS is not fully understood. The objective of this study was to investigate the genetic causes of PCOS by identifying rare variants in genes implicated in its pathophysiology. This was a hospital-based observational study. We used whole-exome sequencing for 52 PCOS women to identify the rare variants in genes related to PCOS pathogenesis. Subsequently, we analysed these variants using in silico prediction software to determine their functional effects. We then assessed the relationship between these variants and the clinical outcomes of the patients. Student's t-test and Fisher's exact test were used to compare clinical parameters and frequency differences amongst PCOS patients with and without variants. A total of four rare exonic variants in obesity- and hyperinsulinaemia-related genes including UCP1 (p.Thr227Ile), UCP2 (p.Arg88Cys), IRS1 (p.Ser892Gly) and GHRL (p.Leu72Met) were identified in eight patients. Significant differences were observed between the patients carrying variants and those without variants. PCOS patients with identified variants exhibited significantly higher average body mass index and fasting insulin levels of PCOS subjects with identified variants compared to those without variants (P < 0.05). Additionally, there were significant differences in the variant frequencies of four variants when compared to the population database (P < 0.05). This study shows a prevalence of rare variants in obesity and hyperinsulinaemia-related genes in a cohort of PCOS women, thereby underscoring the impact of the identified rare variants on the development of obesity and associated metabolic derangements in PCOS women.

IN-SILICO SCREENING OF PHYTOCHEMICAL COMPOUNDS IN CAESALPINIA BONDUCELLA L. SEEDS AGAINST THE GENE TARGETS OF OVARIAN STEROIDOGENESIS PATHWAY

Polycystic ovary syndrome (PCOS) is the most common gynaecological disorder among reproductive-age women. Impaired metabolism of androgens and estrogens is one of the leading causes of PCOS. In India, medicinal herbs are being explored for their anti-androgenic and anti-estrogenic properties. In this study, we have screened the seed extracts of the herbal plant, Caesalpinia bonducella for potent inhibitors of estrogen and testosterone biosynthesis and assimilation. Methanol extract of C. bonducella seed kernels were subjected to gas chromatography - mass spectrometry (GC-MS) to identify the phytochemical constituents. Out of forty-three phytochemical compounds identified from the extract, eight compounds were selected based on Lipinski's rule of five for molecular docking. The selected phytochemical compounds were docked against specific targets of ovarian steroidogenesis pathway; human aromatase (CYP19A1), human 17β-hydroxysteroid dehydrogenase type 1 (HSD17B1), human androgen receptor and estrogen receptor α. Further, the nature of these compounds was validated using density functional theory (DFT) calculations and ADME/T studies. As per the molecular docking output, compounds 33, 35, 38, 40, and 43 exhibited higher binding affinities against the four selected targets. Phytochemical compounds were optimized using Gaussian 16 with the B3LYP function and the 6-31G(d, p) basis set and were correlated with docking results. ADME/T helps in identifying the potential drug candidates from a pool of drugs. Five phytochemical compounds, 33, 35, 38, 40, and 43 were found to have the ability to bind and inhibit appropriate targets in the ovarian steroidogenesis pathway. Hence, these compounds can be further characterized in vitro and in vivo for alleviating PCOS.

A whole-body mystery

New insights into the causes of polycystic ovary syndrome could revolutionise the treatment of this common but neglected condition, reports Alice Klein

The Relation of the SHBG Gene Polymorphism (rs1799941) with PCOS in a Group of Iraqi Women

Polycystic Ovary Syndrome (PCOS) is the most common and complex endocrine disorder that affects women of childbearing age. However, the causes of PCOS are still unknown, however, there is strong evidence supporting the role of genetics in causing it, because PCOS has a strong familial predisposition. More than one gene contributes to the heterogeneous phenotype and clinical and biochemical presentation. Patients with PCOS may complain of irregular menstruation, unwanted hair growth in multiple areas of the body, acne and scalp hair loss, unexplained weight gain, and infertility. This study explores the polymorphism of the SHBG gene locus (rs1799941) in Iraqi women with PCOS that may cause the onset of this disease. Genomic DNA was extracted from blood samples of women with and without PCOS. The SHBG gene was amplified by Tetra_ARMS PCR technology, after which the PCR product was migrated onto the agarose jells at a concentration of 2%. Three genotypes appeared, the homozygous (normal) homozygous GG which is represented by (404 + 270 bp) genotype, the heterozygous (GA) which is represented by (404 + 270 + 210) bp and the homozygous mutant AA genotype. (Which is represented by the bundle (404 + 210 bp). Among the 70 women with PCOS included in the molecular study, (4) of them were carriers of the normal homozygous genotype GG, (44) of them were carriers of the heterozygous genotype GA and (22) were carrying the mutated genotype AA. In the current study, the (OR) value of the mixed GA genotype appeared (12.833) and this indicates that the mixed genotype is a risk factor for the disease, while the (OR) value of the AA mutant genotype was (9.250), and this indicates that the mutant genotype is Homozygous is a risk factor for the disease. The frequency of the A allele was higher in the infection group compared to the control group, and this indicates that the A allele is responsible for the disease association. These results indicated that the locus SHBG gene polymorphism (rs1799941) is associated with PCOS in Iraqi women.

Survey based on classification of PCOS using gene expression

Polycystic ovary syndrome (PCOS) is a complicated endocrine ailment affecting 5–10 % of girls of reproductive age. It is generally has complications such as irregular cycles, hirsutism and polycystic ovaries, collectively with a considerable incidence of insulin resistance. PCOS is taken into consideration a multifactorial ailment with numerous genetic, endocrine and environmental abnormalities. Eventhough, women who are suffered with PCOS are also have chances for cause of metabolic and cardiovascular illnesses and their associated diseases or disorders which are compared to the overall population. PCOS classification done on both phenotype and genotype, based on phenotype it is segmented into four phenotypes as A, B, C, D. This phenotype shows the association between hyperandrogenisms, structure or shape polycystic ovary and immature ovary formation. Phenotypes can be visualized through ultrasound images. Based on genotype, PCOS are categorized into three based on the hormonal factors. By analyze PCOS genetically we early diagnose the syndrome and take necessary remedial actions and also prevent from inheritance to next generations. In this paper, surveys the different genes involved in causes of PCOS and hormone factors associated with the PCOS.

Factors influencing the prevalence of polycystic ovary syndrome (PCOS) in the United Arab Emirates.

Statistics indicate that at least 20-25% of women suffer from PCOS in the Gulf region. Despite its prevalence and negative implications on reproductive, metabolic, and physiological heath the exact cause of PCOS is unknown, in part due to the diversity of symptoms manifested by this disorder. In this review, we investigate causes of PCOS globally and draw on these studies, to determine the potential contributing factors for PCOS pathogenesis in the UAE population. The most frequently identified factors promoting PCOS pathogenesis that may be pertinent to this population include physiological factors such as insulin resistance, vitamin D deficiency, genetic factors, obesity, and anti-mullerian hormone (AMH) levels in the body as well as environmental factors such as air pollution, endocrine disrupting chemicals, and pesticide use. This evidence will help inform healthcare workers and government agencies to set up optimal guidelines for control and awareness of PCOS in the UAE.

The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome.

Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level.

Expression of Serum PSA, Nesfatin-1, and AMH in Patients with Polycystic Ovary Syndrome.

Insulin resistance and hyperandrogenism are the leading causes of polycystic ovary syndrome (PCOS). Therefore, it has great significance to study the expression levels of PSA, nesfatin-1, and AMH. To provide some reference for clinical diagnosis and treatment of polycystic ovary syndrome (PCOS), the expression levels of PSA, nesfatin-1, and AMH in serum of patients with polycystic ovary syndrome (PCOS) were investigated. The experimental group consisted of 200 patients with polycystic ovary syndrome treated in Shanghai Huashan Hospital from July 2018 to July 2019. The control group consisted of 150 healthy women without pregnancy. The PSA, nesfatin-1, and AMH levels in serum were detected by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). The serum levels of prostate-specific antigen (PSA) and anti-Mullerian hormone (AMH) were 16.53 ± 0.67pg/ml and 10.75 ± 4.02pg/ml in the experimental group (PCOS patients), which were significantly higher than those in the control group (3.27 ± 0.43pg/ml and 5.18 ± 1.84pg/ml, respectively), while the inhibitive factors in the experimental group (1.89 ± 0.99mg/ml) were significantly higher than those in the control group (1.10 ± 0.97mg/ml). There was no significant difference in nesfatin-1. The levels of PSA and nesfatin-1, nesfatin-1, and AMH and the levels of PSA and AMH in patients with polycystic ovary syndrome were positively correlated, and the differences were statistically significant. The levels of PSA, nesfatin-1, and AMH in patients with polycystic ovary syndrome of different ages were different, and the differences were significant and negatively correlated with the age increasing. PSA, nesfatin-1, and AMH levels in patients with polycystic ovary syndrome were significantly different from those in control nonpregnant women. There was a certain correlation between the levels of PSA, nesfatin-1, and AMH, and age. The results have specific clinical reference significance for the diagnosis and treatment of patients with polycystic ovary syndrome.

Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

ABSTRACT The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells (GCs) is one of the causes of PCOS. Herein, our study was carried out using RNA-seq to detect the different gene expression levels in ovarian GCs between three patients with PCOS and four normal controls. To verify the RNA-seq data, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. Hedgehog signaling pathway (Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS tissue (PT). The qPCR also indicated that the expression levels of Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PT were significantly higher than those in the normal tissue (NT). Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Through the chromatin immunoprecipitation assay (ChIP), we found that the Gli1-IP-DNA enriched from the granular cells of PCOS patients was higher than that of the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cells. These results suggest that abnormal activation of Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

Mutational Landscape Screening Through Comprehensive In Silico Analysis for Polycystic Ovarian Syndrome-Related Genes.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrinopathy of indistinguishable etiopathogenesis that is liable to entail genetic and environmental machinery synergistically interacting with its phenotypic expression. It has been hypothesized that the environment secondarily interacts with genes to define the quantifiable phenotype in a primary, genetically determined, hyper-androgenic ovarian defect. The severity and prevalence of the disease are escalating due to uncontrolled diet and lifestyle, the influence of multiple environmental factors as well as genetic disorders. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. The mutational landscape analysis scans the entire genes for SNPs which usually occurs more frequently in patients and not in healthy individuals. In this study, an extensive computational analysis of all reported nsSNPs of the 27 selected PCOS-related genes was performed to infer the most pathogenic forms associated with PCOS. As a result, 28 genetic variants from 11 genes were predicted to be most harmful. Results of the present study can be useful for building an integrative genotype-phenotype database for further studies.

The effect of dapsone in testosterone enanthate-induced polycystic ovary syndrome in rat

BackgroundOne of the most common reasons for infertility is polycystic ovary syndrome (PCOS). PCOS is related to metabolic syndrome, weight gain, type 2 diabetes mellitus, and cardiovascular diseases. Some of the causes of PCOS are dysfunction in the hypothalamus-pituitary-ovarian axis, insulin activity as well as over-activity of sympathetic nerves and elevation in serum levels of pro-inflammatory cytokines. Dapsone, a sulfonamide antibacterial agent, has anti-inflammatory effects such as decreasing inflammatory cytokine levels like TNF-α and IL-1β. MethodsPCOS was induced by subcutaneous injection of testosterone enanthate (1 mg/100 g) in 21 days old female rats for 35 days. Then, the MET control received metformin (300 mg/kg/day, orally) for 28 days, and to evaluate the efficacy of dapsone (DAP), the DAP group received (12.5 mg/kg, orally) for 28 days. Then, on the last day of the study, the rats were euthanized and the blood was collected to measure the serum levels of hormones, glucose, LDL, LDL/HDL and the left ovaries were dissected for histopathological assay. ResultsIn the PCOS group, the serum levels of glucose, LDL and LDL/HDL were significantly higher than in the control group (P < 0.001). In addition, the levels of LH, FSH and testosterone changed in the PCOS group compared to the control (P < 0.001). The histopathological morphology changes of the ovary of the PCOS group were significant. Treatment with dapsone and metformin reversed the effects of testosterone in the DAP and MET groups. ConclusionsBased on the data, dapsone displayed a good antiandrogenic role via decreasing the testosterone levels in PCOS-induced rats.

In Search of New Therapeutics-Molecular Aspects of the PCOS Pathophysiology: Genetics, Hormones, Metabolism and Beyond.

In a healthy female reproductive system, a subtle hormonal and metabolic dance leads to repetitive cyclic changes in the ovaries and uterus, which make an effective ovulation and potential implantation of an embryo possible. However, that is not so in the case of polycystic ovary syndrome (PCOS), in which case the central mechanism responsible for entraining hormonal and metabolic rhythms during the menstrual cycle is notably disrupted. In this review we provide a detailed description of the possible scenario of PCOS pathogenesis. We begin from the analysis of how a set of genetic disorders related to PCOS leads to particular malfunctions at a molecular level (e.g., increased enzyme activities of cytochrome P450 (CYP) type 17A1 (17-hydroxylase), 3-HSD type II and CYP type 11A1 (side-chain cleavage enzyme) in theca cells, or changes in the expression of aquaporins in granulosa cells) and discuss further cellular- and tissue-level consequences (e.g., anovulation, elevated levels of the advanced glycation end products in ovaries), which in turn lead to the observed subsequent systemic symptoms. Since gene-editing therapy is currently out of reach, herein special emphasis is placed on discussing what kinds of drug targets and which potentially active substances seem promising for an effective medication, acting on the primary causes of PCOS on a molecular level.

Continuous Light-Induced PCOS-Like Changes in Reproduction, Metabolism, and Gut Microbiota in Sprague-Dawley Rats.

The interplay between genetic and environmental risk factors contributes to the pathogenesis of metabolic disease. Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Circadian rhythm disruption is an important risk factor for PCOS. In this study, we evaluated the effect of circadian disorder on reproduction as well as metabolism, and determined its influence on gut microbiota in a rat model. Female Sprague Dawley (SD) rats were kept under continuous light exposure (12-h:12-h light/light cycle, L/L group) or a control cycle (12-h:12-h light/dark cycle, L/D group) for four consecutive weeks. Manifestations in endocrine hormones and metabolism were detected and gut microbiota were analyzed with the 16s rRNA gene sequencing technique. To our knowledge, this is the first study to report PCOS-like reproductive manifestation, such as anti-Müllerian hormone (AMH) elevation induced by continuous light exposure. Moreover, continuous light resulted in abnormal glucose metabolism and gut microbial community variations, including enrichment of the microbial genus of Parasutterella and reduced abundance of genus Corynebacterium, genus Odoribacter, and genus Acinetobacter. Increased Parasutterella abundance was positively correlated with serum testosterone level. A PICRUSt analysis revealed that reproductive and metabolic-related genes were enriched in rats of L/D group. In conclusion, the present study demonstrates that continuous light exposure, an important environmental factor, contributes to the occurrence and developmental progress of PCOS and changes in microbial component and structure. Continuous light exposure is one of vital causes of PCOS, which is closely related to microbial structure and functions.

Aromatase Gene Polymorphism (rs2470152) in Polycystic Ovary Syndrome Patients of Eastern Uttar Pradesh

Introduction: Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder occurring in fertile age women. Its prevalence is increasing and varies day by day in the present population depending on the diagnostic criteria. The diagnostic features of PCOS are known at least but the causative factors which directly or indirectly play a part in it are yet not known. Few studies have demonstrated that aromatase gene with many factors (hormonal, environmental etc.,) may play a role together for the causes of PCOS. Aim: The purpose of this study was to characterise the salient features, frequency of PCOS in Eastern Uttar Pradesh population and aromatase gene polymorphism (rs2470152) analysis with Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH) as reference gene. Materials and Methods: It was a pilot study where participants were recruited from SS Hospital, BHU between January 2018-2019. Participants completed a questionnaire with proforma and had to undergo physical examination before inclusion in the study. Single Nucleotide Polymorphisms (SNP) analysis was done for aromatase gene by PCR-RFLP. Allele and genotype distribution among groups were evaluated using the chi-square test or Fisher’s-Exact test. Two-tailed p-values less than 0.05 were considered statistically significant.Results: The data indicated that the prevalence of PCOS was high in reproductive age group and hormone profiles differ in different participants, with features of PCOS. With this it was found that aromatase gene was expressed in both control and PCOS patients, but the aromatase gene polymorphism was not significantly related to PCOS. Conclusion: PCOS was increasingly high in reproductive women of eastern Uttar Pradesh population. Its diagnostic criteria have many parameters that differ from individual to individual. The aromatase gene polymorphism is not found significantly associated with PCOS in the Eastern Uttar Pradesh population.

Polycystic ovary syndrome (PCOS) and genetic predisposition: A review article.

Polycystic ovary syndrome (PCOS) is a heterogeneous condition which is related to an endocrine reproductive disorder of females. It affects females of 18–44 age. The persistent hormonal disbalance leads to the complexities such as numerous cysts, an irregular menstrual cycle that ultimately leads to infertility among females. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. It is essential to carry out such studies that identify the clear cause of PCOS and its genetic association and hormonal disbalance. This review has highlighted different genes and their correlation with PCOS that leads to hormonal disbalance. Yet not in-depth but an attempt to study the genetic predisposition of PCOS.