scholarly journals DNA methylation of AMHRII and INSR gene is associated with the pathogenesis of Polycystic Ovary Syndrome (PCOS)

2021 ◽  
Vol 29 ◽  
pp. 11-25
Author(s):  
Xingming Zhong ◽  
Fenpin Jin ◽  
Chuican Huang ◽  
Mengxuan Du ◽  
Mengge Gao ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Polycystic Ovary Syndrome ◽  
Methylation Level ◽  
Polycystic Ovary ◽  
Immunohistochemical Method ◽  
Gene Methylation ◽  
Ovary Syndrome ◽  
Insr Gene ◽  
Pcos Group

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecologic endocrinopathy, characterized by menstrual disorders, ovulation disorders, polycystic ovary, hyperandrogen syndrome and insulin resistance. At present, the etiology and exact pathogenesis of PCOS are still unclear. Anti-Müllerian hormone is a local regulator secreted by ovarian granulosa cells, and participates in regulating the occurrence and development of PCOS. Insulin resistance is another important pathophysiological feature of PCOS. Although the expression of anti-müllerian hormone receptor (AMHR) and insulin receptor (INSR) in PCOS have been previously reported, the DNA methylation of the genes have not been well characterized. OBJECTIVE: To study AMHR II/INSR and its role in gene methylation in Ovarian and endometrial pathology of PCOS subjects. METHODS: We recruited seventy-five women with PCOS as cases and twenty healthy women as controls, using immunohistochemical method, study localization, distribution and expression of MHRII/INSR in ovary and endometrium and then discover the correlation of AMHRII/INSR gene methylation. RESULTS: Different clinical features in PCOS group AMHRII gene methylation level and insulin resistance relations have significant differences (r= 0.532, P= 0.000); INSR gene methylation level and insulin resistance relations have significant differences (r= 0.281, P= 0.03). CONCLUSIONS: The analysis of DNA methylation suggested that methylation of AMHRII and INSR genes was associated with basic clinical characteristics and insulin resistance of PCOS. These results provide evidence for AMHRII and INSR genes, and their methylation levels are intimately associated with the pathogenesis of PCOS.

scholarly journals Adipokine levels and carbohydrate metabolism in patients diagnosed de novo with polycystic ovary syndrome

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Ewelina Kolan′ska-Dams ◽  
Joanna Boinska ◽  
Maciej W. Socha
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Carbohydrate Metabolism ◽  
De Novo ◽  
Polycystic Ovary ◽  
Control Group ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Positive Correlation ◽  
Pcos Group

Introduction: Central obesity appears to play a major role in the pathogenesis of metabolic disorders in polycystic ovary syndrome. Insulin resistance and carbohydrate disorders are associated with dysfunctional secretion of various adipokines by the adipose tissue. Objectives: This study aimed to evaluate leptin, apelin, and visfatin against a background of carbohydrate metabolism parameters in patients diagnosed de novo with polycystic ovary syndrome (PCOS). Material and methods: The study group consisted of 40 patients with PCOS (mean age, 29 years) diagnosed in accordance with the American Society for Reproductive Medicine criteria from 2003. The control group consisted of 37 clinically healthy women (mean age, 26 years). All controls had regular menses and no clinical or biochemical signs of hyperandrogenism. Concentrations of leptin, apelin, visfatin, and insulin were measured by immunoenzymatic methods. Glucose concentrations were determined using spectrophotometry. Results: Significantly higher concentrations of leptin, insulin, homeostatic model assessment for insulin resistance (HOMA-IR) index, and the immunoreactive insulin (IRI)/glucose index were found in the PCOS group than in the control group. Notably, the concentration of apelin was over five times lower in the PCOS group than in the control group. In patients with PCOS, a positive correlation was found between the concentrations of insulin and leptin and concentrations of leptin and IRI/glucose. Patients of the PCOS group with body mass index (BMI) ≥  25 had significantly higher values of leptin, insulin, HOMA-IR index, and IRI/glucose index than patients of the PCOS group with normal BMI. In the PCOS group, a positive correlation was found between BMI and leptin concentration (r = 0.7176; p < 0.0001) and carbohydrate metabolism, such as insulin (r = 0.5524; p = 0.0003), glucose (r = 0.3843; p = 0.0157), HOMA-IR (r = 0.5895; p < 0.0001), and IRI/glucose (r = 0.3872; p = 0.0163). These findings were not observed in the control group. Conclusions: (1) Increased leptin concentration observed in women diagnosed de novo with PCOS as well as positive correlations between leptin and HOMA-IR, and IRI/glucose and BMI may indicate a potential role of leptin in the reduction of tissue sensitivity to insulin. (2) Significantly lower apelin concentration in the PCOS group (>5 fold) than in the control group, associated with a concomitant increase in leptin, may also contribute to carbohydrate metabolism disorders occurring in the course of PCOS.

Astragalus hamosus Acts as an Insulin Sensitizer Through the Treatment of Polycystic Ovary Syndrome Rat Models by Affecting IRS1 Expression

2021 ◽  
Vol 21 ◽  
Author(s):  
Amir Nejati ◽  
Maryam Parvini Kohneh Shahri ◽  
Tarlan Farahvash
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Rat Models ◽  
Qrt Pcr ◽  
Pcos Group ◽  
The Impact

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality among women of reproductive age. Insulin resistance is known as the hallmark of PCOS that leads to hyperinsulinemia and type 2 diabetes in PCOS patients. Objective: This study aimed to evaluate the expression pattern of IRS1 as a candidate gene in insulin resistance development in the PCOS Rat models. Methods: In this study, estradiol valerate was used for PCOS induction. Then, all of the rats were divided into five experimental groups and treated with Astragalus hamosus extract. Ethanol was used for extraction by Soxhlet, and extracts were analyzed by GC-MS. Ovarian morphology was analyzed using histological experiments. Finally, the expression of IRS1 and hormonal titration of testosterone and insulin were evaluated using qRT-PCR and ELISA assays, respectively. Results: Induction of PCOS led to an increase in body weight, which decreased after treatment with the extract. Histological assessment declared an increased number of corpus luteums in treated groups and reduced cystic follicles compared with the PCOS group. Astragalus hamosus extract-treated groups exhibited decreased levels of insulin and testosterone compared to the PCOS group. qRT-PCR results showed an increase in the expression levels of IRS1 in the treated groups compared to the PCOS group. Conclusions: This study indicated the impact of Astragalus hamosus extract on PCOS by clarifying the increased levels of IRS1 expression in the treated groups compared to the PCOS group.

Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome

2019 ◽  
Vol 51 (04) ◽  
pp. 261-266 ◽  
Author(s):  
Meryem Pekcan ◽  
Aytekin Tokmak ◽  
Hatice Akkaya ◽  
Gültekin Pekcan ◽  
Andaç Onur ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Molecular Weight ◽  
Polycystic Ovary Syndrome ◽  
High Molecular Weight ◽  
Polycystic Ovary ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ovary Syndrome ◽  
High Molecular Weight Adiponectin ◽  
Pcos Group ◽  
The Relationship

AbstractThe purpose of this study was to assess the rate of insulin resistance (IR) and the relationship between IR and high-molecular weight adiponectin (HMWA) in patients with polycystic ovary syndrome (PCOS). A cross sectional study involving 43 women with PCOS and 39 normal women was carried out over a period of nine months. Fasting glucose and insulin levels, lipid parameters and androgen levels were measured in all serum samples. HMWA was determined by enzyme-linked immunosorbent assay and IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The IR was more prevalent in the PCOS group than in the controls (p=0.002). Dehydroepiandrosterone sulfate, sex hormone binding globulin, free androgen index, total testosterone, insulin, and HOMA-IR levels were significantly higher in the PCOS group as compared to the control group (all p<0.05). Moreover, HMWA was significantly lower and negatively correlated with the clinical and biochemical hyperandrogenism in the PCOS group. HMWA and HOMA-IR were also associated with triglyceride, body mass index, and fat mass in this group. ROC curve analyses demonstrated that the AUC, indicative of the HMWA value for discriminating PCOS with IR, was 0.725, with a confidence interval of 0.615–0.835 (p=0.001). The serum HMWA levels are lower in patients with PCOS, which suggest that HMWA might be involved in the pathogenesis of PCOS. We also conclude that HMWA might be a strong determinant of IR in PCOS patients.

scholarly journals Serum Asprosin Level in Different Subtypes of Polycystic Ovary Syndrome: A Cross-sectional Study

2020 ◽  
Author(s):  
yonghui jiang ◽  
yue liu ◽  
zhiheng yu ◽  
ping yang ◽  
lei xie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Laboratory Data ◽  
Control Group ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Cross Sectional ◽  
Significant Difference ◽  
Pcos Group

Abstract Objective Polycystic ovary syndrome (PCOS) can be divided into different subtypes, including insulin resistance (IR) and hyperandrogenism (HA). Asprosin is a novel hormone associated with IR; however, the role of asprosin in women with PCOS has not been investigated. Thus, the aim of this study was to investigate the relationship between serum asprosin levels and PCOS subtypes. Methods Ninety-three women with PCOS and 77 healthy women as controls were selected for this study. Clinical and laboratory data were compared between the PCOS group and the control group. The PCOS group was further divided into subgroups: 1) women with or without HA (PCOS HA and PCOS NHA, respectively); 2) women with or without IR (PCOS IR and PCOS NIR, respectively). Serum asprosin was measured by ELISA. Results Serum asprosin levels showed no significant difference between the PCOS and control groups. However, it was significantly lower in the PCOS HA and IR groups compared to the respective PCOS NHA and NIR groups (P < .05). In the PCOS group, serum asprosin was negatively correlated with body mass index, luteinizing hormone, testosterone, basal antral follicles, fasting insulin, Homeostatic Model Assessment of Insulin Resistance, and triglycerides. After adjusting for BMI, the correlations were not significant and asprosin was only positively correlated with prolactin (r = 0.426, P < .001). Conclusions Our study shows that women with PCOS HA or IR exhibit significantly lower serum asprosin levels compared to controls, and the lower asprosin level directly correlated with PRL level.

Luteolin alleviates polycystic ovary syndrome in rats by resolving insulin resistance and oxidative stress

2021 ◽  
Author(s):  
Yue Huang ◽  
Xiang Zhang
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Sprague Dawley ◽  
Ovary Syndrome ◽  
Protein Levels ◽  
Sprague Dawley Rats ◽  
Ovarian Morphology ◽  
Pcos Group

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by elevated secretion of androgen, commonly associated with insulin resistance (IR), which could exacerbate patient with PCOS. Development of a safe and effective treatment in preventing and treating PCOS will be beneficial to women of reproductive age. Female Sprague-Dawley rats were randomly divided into 4 groups: sham group treated with vehicle (saline) or luteolin; letrozole and high fat diet induced PCOS group treated with vehicle or luteolin (25, 50, 100 mg/kg intraperitoneally). Ovary tissue and blood were collected for further analysis. Luteolin normalized estrus cycle and improved ovarian morphology, including reduced polycystic and alleviated the loss of oocytes and corpus luteum in PCOS rats. Serum follicle stimulating hormone, and estradiol were reduced while luteinizing hormone and testosterone were elevated in PCOS rats relative to that of sham, which were significantly normalized by luteolin. Notably, luteolin significantly inhibited IR and up-regulated protein levels of PI3K p85a and pAKT compared with PCOS rats treated with vehicle. In addition, the activities of antioxidants such as SOD, GPx, CAT and GSH were reduced in PCOS rats, which were significantly increased by luteolin. Protein and mRNA expressions of Nrf2 and downstream genes such as Hmox1 and Nqo1 were restored by luteolin in PCOS rats. Collectively, this study demonstrated that luteolin inhibited IR by prompting PI3K/AKT signaling pathway and enhanced antioxidative response through the restoration of Nrf2 pathway.

Lipocalin-2 Level in Patients with Polycystic Ovary Syndrome: Association with Insulin Resistance and Metformin Therapy

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Mohamed Reda Halawa ◽  
Laila Mahmoud Ali Hendawy ◽  
Alaa Sayed Hassanin ◽  
Salah Hussein Ali El Halawany ◽  
Hanem Ibrahim Abdel Fattah Abdel Kader
Keyword(s):  
Insulin Resistance ◽  
Waist Circumference ◽  
Polycystic Ovary Syndrome ◽  
Weight Reduction ◽  
Polycystic Ovary ◽  
P Value ◽  
Lipocalin 2 ◽  
Ovary Syndrome ◽  
Metformin Therapy ◽  
Pcos Group

Abstract Background PCOS appears to be associated with an increased risk of metabolic aberrations, including insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dyslipidemia, and cardiovascular disease throughout womens’ lifespan. Obesity is a state of chronic low-grade systemic inflammation. This chronic inflammation is characterized by abnormal cytokine production and activation of inflammatory signaling pathways in adipose tissues, which contributes to insulin resistance and its related diseases such as PCOS and metabolic syndrome. Objective To evaluate Lipocalin-2 level in a sample of Egyptian females with PCOS and study the effect of metformin therapy on Lipocalin-2 level in patients with PCOS. Methods This case control study was conducted on 52 females, collected from the outpatient obstetrics and gynaecology clinics of Ain Shams University Hospitals from June 2018 to March 2019, their age ranged between 17-43 years old. divided into 2 groups: Group (I) 32 women with polycystic ovary syndrome According to the Rotterdam diagnostic criteria of PCOS, and Group (II) 20 healthy women old with normal ovulatory cycle as a control group. All subjects were subjected to full medical history taking, thorough physical examination including BMI and waist circumference. Fasting plasma glucose, Fasting s.insulin, HOMA-IR, lipocalin-2 level were assessed. Results Serum lipocalin-2 levels did not differ between patients with PCOS and BMI-matched healthy controls (P-value 0.193), and there was no significant difference between the 2 studied groups as regard HOMA-IR (p = 0.375). Metformin therapy for 3 months in patients with PCOS in the present study, resulted in significant reduction in lipocalin-2 level (p-value&lt;0.01), (mean 54.2±15.3ng/ml before metformin therapy vs 42.9±14.2 ng/ml after metformin therapy). Moreover, metformin therapy in PCOS group resulted in significant reduction in weight, BMI, waist circumference and HOMA-IR. Furthermore, linear regression analysis for the parameters affecting lipocalin level in our study, showed that BMI was the only significant confounder affecting lipocalin level. So, the reduction in lipocalin level following metformin therapy in PCOS group in our study may be due to weight reduction perse. Conclusion PCOS per se is not associated with elevated serum lipocalin-2 levels. Metformin therapy induces a significant reduction in serum lipocalin-2 levels, weight, BMI, waist circumference and HOMA-IR in patients with PCOS. Reduction of BMI was the only significant confounder affecting lipocalin level after metformin therapy. So the reduction in lipocalin level following metformin therapy in patients with PCOS in our study may be due to weight reduction perse.

scholarly journals Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome

2018 ◽  
Vol 103 (12) ◽  
pp. 4465-4477 ◽  
Author(s):  
Emma Nilsson ◽  
Anna Benrick ◽  
Milana Kokosar ◽  
Anna Krook ◽  
Eva Lindgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Dna Methylation ◽  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Differentially Expressed ◽  
Ovary Syndrome ◽  
Cpg Sites

Abstract Context Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index‒matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of ∼30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.

scholarly journals Magnolia officinalis Ameliorates Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome in Rats

2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Aline Nassar ◽  
Maha Khachab ◽  
Hayat Zaatiti ◽  
Amjad Kanaan
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Protein Expression ◽  
Polycystic Ovary ◽  
Sesame Oil ◽  
Control Group ◽  
Ovary Syndrome ◽  
Pcos Group ◽  
Magnolia Officinalis

Background: Polycystic ovary syndrome (PCOS) is a prevalent reproductive and metabolic disorder. Insulin resistance (IR) is highly associated with PCOS and aggravates its symptoms. Thiazolidinediones (TZDs), as insulin sensitizing agents, are PPARγ agonists that improve many of the symptoms of PCOS. The Magnolia officinalis extract (MOE) is a natural peroxisome proliferator activated receptor gamma (PPARγ) agonist that improves insulin sensitivity in experimental models. Objectives: Using a dehydroepiandrosterone (DHEA)-induced rat model of PCOS and IR, this study aimed to explore both the potential beneficial effects and the molecular mechanisms of action of MOE. Methods: Post-pubertal female Sprague Dawley rats were subcutaneously injected daily with DHEA (6 mg/100 g body weight) dissolved in sesame oil for 28 days (n = 30). Age- and weight-matched control rats received only sesame oil (n = 12). Afterward, 16 of the DHEA-injected rats, along with five control rats, were sacrificed for blood and tissue collection. The 14 remaining DHEA-injected rats received either treatment of 30 days of oral MOE (500 mg/kg) dissolved in dimethyl sulfoxide (DMSO) (n = 7), or oral DMSO only (n = 7). Meanwhile, the remaining control rats (n = 7) continued to receive daily oral DMSO for 30 days. At the end of the treatments, the rats were sacrificed for blood and tissue collection. Results: After 28 days, the DHEA-treated rats exhibited an increase in body weight as compared to controls (P < 0.05). DHEA injection induced a PCOS phenotype as evident by a statistically significant (P < 0.05) elevated serum luteinizing hormone (LH), and an increased number of cystically dilated follicles with thicker granulosa compared to controls. PCOS rats showed a statistically significant rise in fasting insulin with an increased homeostatic model assessment index of insulin resistance (HOMA-IR) as compared to controls (P < 0.05). Compared to the control group, PCOS rats had a statistically significant lower ovarian protein expression of PPARγ, insulin receptor substrate 1 (IRS1), and protein kinase B (Akt) by Western Blot (P < 0.05). Conversely, the PCOS group showed an increased mammalian target of rapamycin (mTOR) pathway activity as evident by an increase in the fraction of phosphorylated mTOR to total mTOR compared to the control group (P < 0.05). When treated for 30 days with oral MOE (500 mg/kg), the PCOS rats showed a statistically significant decrease in body weight and serum LH levels as compared to the non-treated PCOS rats (P < 0.05). The number of cystically dilated follicles in the MOE-treated PCOS rats was significantly reduced compared to the non-treated PCOS rats. In the MOE-treated PCOS rats, the ovarian protein expression of PPARγ, IRS1, and Akt was significantly increased, while the p-mTOR/mTOR expression was decreased compared to the non-treated PCOS group (P < 0.05). Conclusions: According to our results, the MOE ameliorated the DHEA-induced PCOS phenotype histologically, hormonally, and metabolically. Fundamentally, this explores the elusive pathophysiologic association between IR and PCOS by targeting pathways common to both disorders.

Evaluation of the pathophysiological role of Fetuin A levels in adolescents with polycystic ovary syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elvan Bayramoğlu ◽  
Semra Çetinkaya ◽  
Servan Özalkak ◽  
Erdal Kurnaz ◽  
Gülşah Demirci ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Ovary Syndrome ◽  
Fetuin A ◽  
Pathophysiological Role ◽  
Pcos Group ◽  
Natural Inhibitor

Abstract Objectives Polycystic ovary syndrome (PCOS) is an endocrinopathy, in which hyperandrogenism and hyperinsulinism have both occurred. Fetuin-A, a natural inhibitor of tyrosine kinase, leads to insulin resistance. The aim was to evaluate the relationship between fetuin-A and hyperandrogenism and hyperinsulinism and the role of fetuin-A in the pathophysiology of PCOS. Methods Thirty-eight cases with PCOS and 40 healthy adolescents were included in the study. PCOS and controls were divided into obese/non-obese subgroups. LH, FSH, total and free testosterone (TT, FT), SHBG, androstenedione, DHEAS were measured in patients with PCOS. Fasting glucose, insulin, lipid profile, AST, ALT, HsCRP, and fetuin levels of PCOS patients and healthy controls were also measured. Results Fetuin-A levels were higher in PCOS patients than in controls. In the obese-PCOS group, when compared to non-obese PCOS patients; the levels of SHBG and HDL were low while cholesterol, LDL, triglyceride, HOMA-IR, FT, FAI, and HSCRP levels were high, but Fetuin-A levels were similar. In the obese-PCOS group, fetuin-A levels were higher than in obese-controls. HOMA-IR and fetuin-A levels were higher in non-obese PCOS patients than in non-obese controls. In the PCOS group, fetuin-A was positively correlated with TT, FT, FAI and androstenedione and negatively correlated with SHBG. Regression analysis demonstrated that FT, SHBG, and androstenedione significantly predicted fetuin-A levels (R2=54%). In non-obese PCOS patients and controls, fetuin-A was positively correlated with insulin and HOMA-IR. Conclusions These results suggest a relationship between androgen levels and fetuin-A in PCOS cases, independent of insulin resistance, and may shed light on further studies.

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