scholarly journals Investigation of Therapeutic Effects of Erdosteine on Polycystic Ovary Syndrome in a Rat Model

2018 ◽  
Vol 27 (6) ◽  
pp. 515-522 ◽  
Author(s):  
Atilla Karateke ◽  
Recep Dokuyucu ◽  
Hatice Dogan ◽  
Tumay Ozgur ◽  
Zeynel Abidin Tas ◽  
...  

Objective: Polycystic ovary syndrome (PCOS) is a serious endocrine disorder. In the present study, we investigated the therapeutic effects of erdosteine in letrozole-induced PCOS in rats. Methods: Thirty-two Wistar albino female rats were grouped as control group (C), PCOS group (PCOS), PCOS-metformin group (PCOS+MET), and PCOS-erdosteine group (PCOS+Erd). PCOS was induced by administering letrozole; such rats presented with sex hormone disorder, abnormal estrous cycles determined by daily vaginal smear, large cystic follicles, and increasing fasting insulin levels. After induction of PCOS, metformin (500 mg/kg/day) and erdosteine (100 mg/kg/day) were given orally to the treatment groups for 30 days. Serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, circulating estrone (E1), estradiol (E2), testosterone, and androstenedione were evaluated. The ovaries were graded histologically. Results: Weights of ovarian tissues (p < 0.05) and the number of atretic follicles (p < 0.001) and cystic follicles (p < 0.01) decreased in the PCOS+Erd group; the corpus luteum number was significantly higher in the PCOS+Erd group (p < 0.01) as compared with the PCOS group. Lipid parameters (total-C, LDL-C, and TG), E1 (estrone), E1/E2 ratio, testosterone, and androstenedione significantly decreased, while HDL-C and E2 (estradiol) significantly increased in the PCOS+Erd group as compared with the PCOS group. Moreover glucose, insulin, and HOMA-IR were reduced with treatment of erdosteine (p > 0.05, p < 0.001, and p < 0.001, respectively). Conclusion: It is suggested that erdosteine may be used in the treatment of PCOS as an alternative to metformin. It appears that our findings might be supported by clinical and molecular studies.

2020 ◽  
Vol 8 (A) ◽  
pp. 517-520
Author(s):  
Hilma Putri Lubis ◽  
Muhammad Fidel Ganis Siregar ◽  
Ichwanul Adenin ◽  
Binarwan Halim ◽  
Henry Salim Siregar ◽  
...  

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders of women in the childbearing period. However, its pathophysiology is still unclear. Certain polymorphisms of the luteinizing hormone/choriogonadotropin receptor (LHCGR) genes may lead to changes in the bioactivity of this hormone. The important functional role of LHCGR in the metabolism of androgen and ovulation, the LHCGR gene variant, may be related to the risk of PCOS. AIM: The aim of this study was to evaluate the association between LHCGR Ins18LQ gene polymorphism and PCOS. METHODS: A case–control study was performed in women with PCOS and non-PCOS from May 2019 to October 2019 in HFC IVF Center. We included 50 women with PCOS and 50 healthy controls. Polymorphism of the LHCGR (ins18LQ) gene was genotyped using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: From this study, we found that there was no significant difference in the proportion of ages between the groups (p > 0.05). There were significant differences in the characteristics of body mass index, FSH level, LH level, and LH/FSH ratio between the PCOS and control groups (p < 0.05). We also found that the proportion of heterozygote variant non-ins/ins was higher in the PCOS group compared to the control group, but there was no significant difference between the polymorphisms of the non-ins and non-nonins variants between the PCOS and control groups (p = 0.269). The frequency of ins alleles was higher in the PCOS group compared to the control group. CONCLUSION: There was no significant association between LHCGR ins18LQ gene polymorphism and PCOS.


2019 ◽  
Vol 3 (5) ◽  

Neuropeptides coordinate and regulate physiological processes in all animals. Alarin is a 25 amino acid neuropeptide which promotes the secretion of luteinizing hormone (LH). It has been known that serum luteinizing hormone levels are increased in women with polycystic ovary syndrome. Therefore, purpose of this was to examine the association of circulating gonadotropin secretions, and alarin with women with polycystic ovary syndrome, and to compare these findings with those of control subjects in an effort to better understand the pathophysiology of PCOS. 28 participants with a diagnosis of PCOS with normal weight and 28 participants with a diagnosis of PCOS with obese and 28 control group participants were included in this case-control study. Hormone profiles of the participants (alarin, insulin, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-SO4 ), lipid profiles total testosterone, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol) and fasting blood sugar (FBS) values were measured. Results: Serum androgens were elevated in the PCOS. Blood LH was also elevated (P < 0.05) but was higher in PCOS than Control. Patients with PCOS had an increased alarin compared with controls. LH/FSH ratio and Alarin /FSH ratio were greater than 2.1, 2.4, respectively. The blood alarin levels were significantly correlated with the serum LH levels (r=0.492, p=0.002) and the LH/FSH ratios (r=0.450, p<0.001) and Alarin/ FSH ratios. The FSH/LH and alarin /FSH ratio were elevated in the PCOS. Based on these results, the FSH/LH and Alarin /FSH ratio appears to be a useful marker of PCOS.


2020 ◽  
Vol 23 (2) ◽  
pp. 25-34
Author(s):  
Sipel Younis Mustafa ◽  
Shereen. A. Ibrahim

Background and Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 10–15 % of women in reproductive age. The objective was to evaluate the effect of irisin in the etiology of obese patient with PCOS. Study Design and Methods: The study design its a case control study. This study involved fifty obese ladies (50) with confirmed diagnosis of PCOS. The second group served as control group and included forty apparently normal (non-polycystic ovary) obese ladies (40). The following main parameters were measured: Fasting serum levels of total Cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein– cholesterol, glycohaemoglobin (HbA1c%), Insulin , Testosterone, FSH, serum LH and Irisin. Results: The median serum Irisin was significantly higher among PCOS cases (119.1 ng/ml) compared to healthy controls (74.7 ng/ml). The median serum FSH was significantly higher among PCOS cases (6.52 ng/ml ) compared to controls (4.72 ng/ml). Serum LH was obviously higher among PCOS cases (6.88 ng/ml) compared to controls (6.08 ng/ml). The mean pulse rate, blood WBC count and serum VLDL were significantly higher (71.6/min, 8.3 mg/dl and 22.5 mg/dl respectively) in cases with PCOS compared to controls (67.5/min, 7.2 mg/dl and 18.5 mg/dl respectively). Conversely, the serum HDL was significantly lower among PCOS cases (43.8 mg/dl) compared to controls (48.4 mg/dl), serum testosterone showed statistically non-significant differences. Conclusion: Data of the present study showed that serum Irisin was significantly higher among PCOS cases. These findings suggest important role of irisin as a biomarker for PCOS and an important factor in the development of PCOS.


2010 ◽  
Vol 299 (4) ◽  
pp. E551-E559 ◽  
Author(s):  
Julia Johansson ◽  
Yi Feng ◽  
Ruijin Shao ◽  
Malin Lönn ◽  
Håkan Billig ◽  
...  

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance, possibly reflecting defects in skeletal muscle and adipocyte insulin signaling. Low-frequency (2 Hz) electroacupuncture (EA) increases insulin sensitivity in female rats with dihydrotestosterone (DHT)-induced PCOS, but the mechanism is unclear. We hypothesized that low-frequency EA regulates mediators involved in skeletal muscle glucose uptake and metabolism and alters the lipid profile in rats with DHT-induced PCOS. To test this hypothesis, we implanted in prepubescent female rats 90-day continuous-release pellets containing DHT (PCOS). At 70 days of age, the rats were randomly subdivided into two groups: one received low-frequency EA (evoking muscle twitches) for 20–25 min five times/wk for 4–5 wk; the other did not. Controls were implanted with pellets containing vehicle only. All three groups were otherwise handled similarly. Lipid profile was measured in fasting blood samples. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp, soleus muscle protein expression of glucose transporter 4 (GLUT4), and phosphorylated and nonphosphorylated Akt, and Akt substrate of 160 kDa was determined by Western blot analysis and GLUT4 location by immunofluorescence staining. PCOS EA rats had normalized insulin sensitivity, lower levels of total high-density lipoprotein and low-density lipoprotein cholesterol, and increased expression of GLUT4 in different compartments of skeletal muscle compared with PCOS rats. Total weight and body composition did not differ in the groups. Thus, in rats with DHT-induced PCOS, low-frequency EA has systemic and local effects involving intracellular signaling pathways in muscle that may, at least in part, account for the marked improved insulin sensitivity.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yanna Ban ◽  
Haiying Ran ◽  
Ying Chen ◽  
Li Ma

Abstract Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this pilot study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight. Methods Follicular fluid samples were collected from patients who underwent IVF, including normal-weight women without PCOS (control group, n = 10) and normal-weight women with PCOS (PCOS group, n = 8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. Results All 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC < 0.67, p-value < 0.05 and VIP value > 1. These differential species of lipid belong to lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI). Conclusion The identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal-weight.


2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Ziyu Zhang ◽  
...  

Abstract The molecular mechanism that triggers polycystic ovary syndrome is mysterious. Abnormal ovarian granulosa cells are one of the causes of PCOS. Therefore, we carried out RNA-seq in ovarian granulosa cells from patients with PCOS and normal controls and found that Hedgehog signaling pathway members Ihh and ptch2 were abnormally highly expressed in the PCOS group. Granulosa cells from 22 patients with PCOS and 21 controls with normal ovulation were collected. Subsequent qPCR tests also indicated that the expression of ptch1, gli1, and gli2 of other downstream members of Hh in the PCOS group was significantly higher than that in the control group. These results indicate that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.


2015 ◽  
Vol 6 (2) ◽  
pp. 67-72
Author(s):  
Manizheh Karami ◽  
Fatemeh Lakzaei ◽  
MohammadReza Jalali Nadoushan

ABSTRACT Background and objective Polycystic ovary syndrome (PCOS) can be induced in Wistar rats by over production of nitric oxide (NO). This study evaluated the efficacy of naloxone on the breeding characteristics of rats suffering from nitric oxide induced PCOS. Materials and methods Twenty-four female Wistar rats(200–250 gm) were kept as virgin under standard conditions. They were divided into four groups (n = 6). One group of the animals received L-arginine (50 mg/kg) intraperitoneally (i.p.) for 9 days/once a day. Another group was administered naloxone hydrochloride (0.4 mg/kg, i.p.) prior to injection of L-arginine. The third group was injected solely naloxone. Control group received saline solution (1 ml/kg, i.p.). After the treatments, all female rats were coupled with the intact males. They were then separated by observation of vaginal plaques; it was considered as day 0 of pregnancy. Eventually, they were operated on days 18 to 19 of the gestation to collect the animals’ ovaries. The samples were studied for pathological evidence. The fetal number and weight along with the fetal crown-rump length (CRL) were measured. Results The ovaries obtained from the L-arginine treated group had large cysts with thickened granulosa cell layer in contrast to those of the control or naloxone treated rats (p < 0.0001). The number of fetus though showed a decrease in the L-arginine treated rats (3 ± 1), but the fetal weight or fetal CRL did not change (p > 0.05). Conclusion This study may clearly illustrate the polycystic characteristics in the L-arginine treated group. It may particularly display the breeding efficacy of naloxone in rats with PCOS. How to cite this article Karami M, Lakzaei F, Nadoushan MRJ. Naloxone Breeding Effectiveness in Rat Suffering from Nitric Oxide-induced Polycystic Ovary Syndrome. Int J Infertil Fetal Med 2015;6(2):67-72.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mariela Edith Velazquez ◽  
Andrea L. Millan ◽  
Mailén Rojo ◽  
Giselle Adriana Abruzzese ◽  
Silvina Ema Cocucci ◽  
...  

BackgroundPolycystic Ovary Syndrome (PCOS) often present metabolic disorders and hyperandrogenism (HA), facts that may influence the telomere length (TL).AimsTo compare the absolute TL (aTL) between women with PCOS and control women, and their association with the presence of obesity and HA parameters.Materials and methodsThe PCOS group included 170 unrelated women outpatients and the control group, 64 unrelated donor women. Anthropometric, biochemical-clinical parameters and androgen profile were determined. The PCOS patients were divided accordingly to the presence of obesity and androgenic condition. The aTL was determined from peripheral blood leukocytes by Real Time quantitative PCR.ResultsWomen with PCOS exhibited a significantly longer aTL than controls after age adjustment (p=0.001). A stepwise multivariate linear regression in PCOS women, showed that WC (waist circumference) contributed negatively (b=-0.17) while testosterone levels contributed positively (b=7.24) to aTL. The non-Obese PCOS (noOB-PCOS) presented the longest aTL when compared to controls (p=0.001). Meanwhile, the aTL was significantly higher in the hyperandrogenic PCOS phenotype (HA-PCOS) than in the controls (p=0.001) and non hyperandrogenic PCOS phenotype (NHA-PCOS) (p=0.04). Interestingly, when considering obesity and HA parameters in PCOS, HA exerts the major effect over the aTL as non-obese HA exhibited the lengthiest aTL (23.9 ± 13.13 Kbp). Conversely, the obese NHA patients showed the shortest aTL (16.5 ± 10.59 Kbp).ConclusionsWhilst a shorter aTL could be related to the presence of obesity, a longer aTL would be associated with HA phenotype. These findings suggest a balance between the effect produced by the different metabolic and hormonal components, in PCOS women.


2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Ewelina Kolan′ska-Dams ◽  
Joanna Boinska ◽  
Maciej W. Socha

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.


2021 ◽  
Author(s):  
Yaping Jiang ◽  
Rui Jiang ◽  
Peng Zhang ◽  
qiong Yu ◽  
Hongping Ba ◽  
...  

Abstract Purpose To investigate the changes of human granulosa cell, TNFR1, TNFR2 and their downstream molecules in patients with polycystic ovary syndrome (PCOS) and the control group. Methods We recruited infertile women with polycystic ovary syndrome (n = 30) and compared them with infertility due to fallopian tube obstruction(n = 30, control group). The ovaries were stimulated with GnRH agonists and gonadotropins. Follicular fluid from large follicles ([14 mm]) was pooled and granulosa cells (GCs) were separated by a cellular filter. The TNF-α level of follicular fluid was measured by ELISA. TUNEL assay were used to detect the apoptosis of purified GCs. Real-time PCR and Western blotting were used to detect the expression of TNF-related signaling molecules in GCs. Results The rate of high quality embryos in the PCOS group was lower than that in the control group. There were higher percentages of apoptosis in GCs of PCOS patients than in the control group. TNF-α is upregulated in follicular fluid of PCOS patients. TNFR1 and caspase-3 mRNA level were signifificantly higher in PCOS group than in the control group. TNF-α-mediated apoptosis of PCOS granulosa cells was mainly dependent on TNFR1.The TNF-α/TNFR1 signaling pathway mediates apoptosis rather than survival in cumulus cells of PCOS patients. Conclusions TNF-α expression was upregulated in follicular fluid of PCOS patients, and TNFR1 overexpression in female granulosa cells of PCOS was associated with higher levels of apoptosis in these cells, suggesting that the TNF-α/TNFR1 signaling pathway may be a candidate for higher apoptosis in female granulosa cells of PCOS.


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