Therapeutic Effects of Phytoestrogen Naringenin in Polycystic Ovary Syndrome (PCOS): Involvement of Kisspeptin and Calcitonin Gene Related Peptide Signalling Pathways.

A variant in the fibrillin-3 gene is associated with TGF-β and inhibin B levels in women with polycystic ovary syndrome

Analysis of meiotic abnormalities of in vitro matured oocytes from stimulated cycles of non-obese endometriotic and pcos patients: a pilot study

To investigate the expression of peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α) in the ovarian tissue of polycystic ovary syndrome (PCOS) rat model and obese PCOS rat model, and the possible mechanism of PCOS. Thirty SD rats were randomly divided into control group, PCOS rat model group and obese PCOS rat model group. DHEA dissolved in 0.2 mL soybean oil was injected daily into the rats of two PCOS groups for 21 d. Rats in obese PCOS model group were added with high-fat diet based on DHEA modeling, and each group had 10 rats. Body mass were measured before and on the 22 nd day after modeling. The serum testosterone (T) levels were measured by abdominal aortic blood, and the ovarian tissues of rats were taken for histological changes were observed by HE staining, immunohistochemical staining and Western blot to detect PGC-1ɑ protein expression. The body mass of rats in each group increased after modeling, and the body mass of rats in PCOS group and obese PCOS group increased significantly ( P<0.05). The serum T concentration of two PCOS model groups was higher than that of control group ( P<0.01). The serum T concentration in obese PCOS model group was higher than that in the PCOS group ( P<0.05). The results of HE staining of rat ovarian tissue showed that there were follicles and a small amount of corpus luteum at different developmental stages in the control group, and the granulosa cells were arranged in 4-6 layers. The number of immature small follicles in the two PCOS groups was significantly increased. The granulosa cells were arranged in 1-3 layers, relatively looser, and some follicles were atresia. In the obese PCOS group, the diameter of ovarian atretic follicles increased, the number of granulocyte layers decreased, and oocytes disappeared more obviously. Immunohistochemical staining showed that the PGC-1ɑ protein was mainly expressed in the cumulus and granulosa cells of ovarian tissue in the control group. The mean gray level of PGC-1ɑ protein expression in PCOS group (0.53±0.06) and obese PCOS group (0.36±0.03) was lower than that of the control group (0.75±0.03), with the statistical difference ( P<0.05). PGC-1ɑ expression in the obese PCOS group was lower than that in the PCOS group ( P<0.01). The results of Western blot were consistent with those of immunohistochemical staining. PGC-1ɑ is associated with damage of ovarian granulosa cells in high-fat environment. The decrease of PGC-1ɑ expression in granulosa cells of ovarian follicles may be an important cause of PCOS development.

Polycystic ovary syndrome (PCOS) is a status that impact a woman’s hormone levels.A total of (128) samples was divided into four groups (Obese with PCOS, low weight with PCOS ,Obese without PCOS ,and Healthy control) collected from Kamal Al-Samarraiehospital, Ministry-of Health in Baghdad-Iraq during the period of April 2017- August 2017. The aim of the study toevaluation from Serum AdiponectinIrisin and Apelin in Iraqi obese women patients with PCOS. The result shows The BMI of obese with PCOS patients and obese without PCOS was significantly higher (P&lt;0.05) when compared to the values of the control group. No significant with other groups ,also Significant increase of Prolactin (p&lt;0.05) in Obese with PCOS and low weight with PCOS groups in relation to Obese without PCOS and control groups. A non- significant elevation (p&gt;0.05)when comparing between Obese without PCOS, and control groups. The levels of FSH , LH and Testosterone showed significantly change(p&lt;0.05) in Obese with PCOS and low weight with PCOS groups when comparing with Obese without PCOS and control group. followed by no-significant with other groups ,also shows significant change(p&lt;0.05)when comparing between Obese without PCOS and control group ,showed that adiponectin level showed a significant higher level in the control group ,Obese without PCOS group ,low weight with PCOS patients ,and Obese with PCOS patients . Oppositely, the results of the Irisin showed a significant higher level in the Obese with PCOS patients then the low weight with PCOS group followed by the Obese without PCOS and control group. While Apelin level recorded the highest level Obese with PCOS group.

Study question Does serum Kisspeptin (KP) levels discriminate between fertile and infertile women with polycystic ovary syndrome (PCOS)? Summary answer Serum KP levels can be used as a potential discriminatory biomarker for infertility in women with PCOS. What is known already PCOS is the most common cause of anovulatory infertility and not fully elucidated pathology. A persistent rapid gonadotropin-releasing hormone (GnRH) pulse frequency in patients with PCOS exist throughout ovulatory cycle. KP is a neuropeptide that increases GnRH pulsatile release during ovulation. Therefore, KP may have a key role as a central regulator of fertility in PCOS patients. Although, recent studies showed that the KP concentration is higher in PCOS patients, the evidence is limited as to whether serum KP levels determine infertility in PCOS. Study design, size, duration This was a single center prospective cohort study conducted at Goztepe Prof. Dr. Suleyman Yalcin City Hospital Affiliated to Istanbul Medeniyet University, Istanbul, Turkey between January 2023 to February 2023. Our study enrolled 30 fertile and 30 infertile women with PCOS, who were aged between 18 and 45 years. PCOS was defined according to the criteria of the Rotterdam ESHRE- ASRM sponsored consensus group (2004). Participants/materials, setting, methods Venous blood samples from the participants were obtained after fasting and between 8 a.m. and 10 a.m. on days 2-5 of the menstrual cycle. Samples were thawed, and a human KISS1 (Kisspeptin 1) ELISA kit (Elabscience, USA,lot no:E-EL-H5618) was applied to measure KP serum concentrations. Patient characteristics and KP concentrations were compared among the two groups. Statistical analysis was performed by Mann-Whitney, Spearman correlations, and linear regression analysis. A p-value &amp;lt;0.05 was considered significant. Main results and the role of chance The mean age of the patients was 27.57±5.39 years in the fertile PCOS group and 26.80± 4.85 years in the infertile PCOS group (p = 0.63). There was no significant difference among the groups in terms of body mass index (BMI), duration of infertility, serum FSH, LH, LH-to-FSH ratio, E2, antimullerian hormone (AMH), TSH, prolactin, 17OHP, total testosterone, SHBG, HbA1c, HOMA-IR, neutrophil–lymphocyte ratio levels and antral follicle count (AFC). DHEA-S was significantly higher in the infertile PCOS group (306.73±94.869 mcg/ dL), compared to the fertile PCOS group (258.08±84.29 mcg/ dL, p = 0.037). The mean KP level was significantly higher in the infertile PCOS group (444.80±136.61 ng/ mL), compared to the fertile PCOS group (333.02±131.10 ng/ mL, p = 0.001). The KP level was positively correlated with AFC, AMH, and total testosterone levels (R = 0.495, R = 0.548, R = 0.362, p &amp;lt; 0.05, respectively) in the infertile PCOS group. Furthermore, ROC analysis showed that the optimal cut-point value was found to be 285.59. When this cut-off value of serum KP levels was taken, the sensitivity was 0.96 and the specificity was 0.50. Linear regression analysis revealed that AMH was positively associated with KP levels (p = 0.022). Limitations, reasons for caution Due to the limited number of women with available samples, we were not able to analyze KP serum levels according to specific PCOS phenotypes Wider implications of the findings Serum KP levels are higher in infertile women with PCOS compared to fertile women with PCOS. Infertility caused by PCOS can be predicted by serum KP levels. In the future identification, KP in PCOS may be applied to develop potential therapeutic agents. Trial registration number Not applicable

Background: Polycystic ovary syndrome (PCOS) is characterized by polycystic ovarian follicle morphology, ovulatory dysfunction, hyperandrogenism and insulin resistance. Spexin has a role in satiety control, lipid and glucose metabolism. Metformin is an insulin sensitizing agent that has some hepato-protective functions. Aim: This study aimed to declare and compare the effect of spexin and metformin treatment on ovarian and liver function changes in letrozole-induced PCOS in rats and the possible mechanisms involved.Methods: Thirty-two adult female Wistar albino rats divided into control, polycystic ovary syndrome (PCOS), PCOS metformin-treated, and PCOS spexin-treated groups. In PCOS groups, rats were given oral letrozole 0.5 mg/kg dissolved in 0.9% NaCl once daily along the study. In PCOS metformin-treated group, rats were treated with metformin hydrochloride orally (300 mg/kg/day) for the last 4 weeks. In PCOS spexin-treated group, rats were treated with spexin i.p. 35 μg/kg/day, dissolved in normal saline for the last 4 weeks. Results: In PCOS group, there was a significant increase in; BMI, relative ovarian weight, HOMA-IR, serum (LH, FSH, testosterone, insulin, glucose, TC, TG, LDL, ALT, AST, alkaline phosphatase, total & direct bilirubin) and hepatic (MDA, NO & TNF-), with a significant decrease in; serum [estradiol, progesterone, HDL, albumin and spexin] and hepatic GPX, when compared with the control group. Histopathological results showed ovaries of PCOS marked expression of caspase-3 and P53 and decreased KI67 expression of granulosa and theca cells. Vacuolated hepatocytes, dilated and congested portal vein and positive reaction of immunostaining with αSMA, caspase and TNFα. Treatment of PCOS rats with either metformin or spexin reversed these changes significantly.Conclusion: Spexin serum level could be used as a metabolic biomarker for polycystic ovary syndrome. Also, treatment with either metformin or spexin ameliorated ovarian and hepatic dysfunctions in rat model of PCOS through their insulin sensitizing, anti-oxidant and anti-inflammatory effects.

Variation in metabolic and cardiovascular risk in women with different polycystic ovary syndrome phenotypes

IL-22 and its interaction with amino acid and glycolipid metabolite in polycystic ovary syndrome (PCOS) patients

Polycystic ovary syndrome (PCOS) is the most common cause of infertility associated with metabolic complications. Several classes of pharmacological agents have been used to manage PCOS. These drugs have shown adverse effects. Various studies showed the bee pollen (BP) as a substance rich in phytoestrogens. This study aimed to investigate the effects of BP and metformin alone and in combination with proliferation and apoptosis of granulosa cells in the rat model of PCOS. In this experimental study, 54 Wistar rats (180-210 g), was injected 2mg of estradiol valerate intramuscularly and six rats were considered as control. After 60days, the rats were divided into control, sham, and experimental groups. The rats were treated with bee pollen (50, 100, and 200mg/kg) and metformin (300mg/kg), either individually or in combination. Ovarian histology assessment was examined by H&E staining. The serum levels of NO and TNF-α were evaluated. The expressions of P53 and Ki67 were measured by IHC. In the BP and metformin-treated PCOS group, the preantral and antral follicles increased, and cystic follicles significantly decreased (p<.01). The levels of TNF-α, NO, as well as the expressions of Ki67 were decreased in the treated groups compared to the PCOS group (p<.01). On the contrary, apoptosis increased in the groups treated with BP compared to the untreated group (p<.01). BP individually or synergistically with metformin improved the symptoms of PCOS.

Background and Aims: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disease in females of reproductive age and is a significant infertility cause. Inflammation plays a crucial role in the pathogenesis of PCOS. The present study evaluated whether sitagliptin, dipeptidyl peptidase-4 inhibitor, attenuates inflammatory markers C-reactive protein (CRP), interleukin(IL)-6, tumor necrosis factor-α (TNF-α), IL-1β, and transforming growth factor-β (TGF-β) in a rat model of PCOS.&#x0D; Materials and Methods: Twenty-two female adult Wistar rats were randomly divided into four groups: control, PCOS model, PCOS+sitagliptin (25 mg/kg), and PCOS+sitagliptin (50 mg/kg). PCOS was induced by injection of estradiol valerate, intraperitoneally. Sitagliptin was gavaged daily for 30 days to both groups of animals. After the treatment period, blood and ovaries tissue were collected to analyze inflammatory parameters.&#x0D; Results: The mRNA levels of IL-6, IL-1β, TGF-β, and TNF-α in the PCOS model group were markedly elevated compared with the control group (p&lt;0.01). These parameters' mRNA levels were reduced in the sitagliptin treatment groups compared with the PCOS group (p&lt;0.01). Also, the serum concentration of CRP in the PCOS group was more than the control. This increase significantly decreased in groups treated with sitagliptin compared with the PCOS group.&#x0D; Conclusion: The presented study suggested that the protective effects of sitagliptin on PCOS may be due to its inhibitory effect on expression and inflammatory markers' levels.

Objective:Polycystic ovary syndrome (PCOS) is an endocrine system disruption that affects 6-10% of women. Some studies have reported the effect of Vitex agnus-castus (Vitagnus) on the hypothalamic-pituitary-gonad axis (HPG). This study was conducted to investigate Vitagnus effect on the expression of kisspeptin gene in a rat model of PCOS. Materials and Methods:Thirty-two female rats were distributed into: control, Vitagnus-treatment (365 mg/kg for 30 days), PCOS (Letrozole for 28 days) and PCOS animals treated with Vitagnus (30 days of Vitagnus after PCOS induction). At the end of the treatments, serum and ovaries were collected for analysis. Expression level of KISS-1 gene in the hypothalamus was investigated, using Real-Time-PCR. Results:In the PCOS group compared to control, FSH, progesterone and estradiol levels were decreased, whereas testosterone and LH levels were significantly increased. No significant changes were observed in the Vitagnus-treated animals in compare to control. However, Vitagnus treatment in the PCOS group, resulted in a raise in progesterone, estrogen and FSH levels and a reduction in the levels of testosterone and LH. Quantitative gene expression analysis showed that PCOS induction resulted in over-expression of KISS-1 gene, however, Vitagnus treatment reduced this up-regulated expression to normal level.Conclusion:In conclusion, our results indicated that Vitagnus extract inhibited downregulation of KISS-1 gene in the hypothalamus of PCOS rats. Because of the master role of kisspeptin in adjusting the HPG axis, Vitagnus is likely to show beneficial effects in the treatment of PCOS via regulation of kisspeptin expression. This finding indicates a new aspect of Vitagnus effect and may be considered in its clinical applications.

Kisspeptin (KP), a hypothalamic peptide, is known as an important marker for neuroendocrine regulation during the human reproduction process. The unexplained infertility (UI) group comprised 30 patients, polycystic ovary syndrome (PCOS) group comprised 29 patients and the male factor infertility (MFI) group comprised 27 patients. An observational cohort study was conducted. The basic characteristics of the study population, BMI, and serum FSH, LH, E2, AMH, KP, TSH, and PRL levels and antral follicle count (AFC) on the 3rd menstruation day were evaluated. The mean KP level was 281.98 ± 73.9 ng/ml in the UI group, 525.49 ± 164.17 ng/ml in the PCOS group, and 354.313 ± 111.38 ng/ml in the MFI group (p < .001). KP levels were significantly higher in the PCOS group than in the UI and MFI groups (p < .001 for both). AUC was 83% (95% CI: 73%–93%), with 375.15 (pg/ml) as the cutoff value in the PCOS group with 83% sensitivity and 79% specificity. UI may be treated by KP injection therapies and higher levels of KP may be a reliable marker for AFC and diagnosis of PCOS. Clinical Trials registration number: NCT03018314

The aetiology of impairments in autonomic modulation of heart rate variability (HRV) in polycystic ovary syndrome (PCOS) remains unclear, as does the impact of aerobic physical training (APT) on controlling endocrine-metabolic disorders and HRV. This is because these women often present excess body fat. Therefore, we assessed whether the dysregulation in autonomic modulation of HRV in women with PCOS is due to endocrine-metabolic disorders and whether the combination of excess body fat with endocrine-metabolic disorders amplifies cardiovascular autonomic deficits. We also investigated whether APT positively influences autonomic modulation of HRV in PCOS. Non-randomised clinical trial. Women with and without PCOS with different percentages of body fat. Participants were divided into four groups: women without PCOS with a body fat percentage between 22% and 29% (CONTROL group; 22%-29%); CONTROL (30%-37%) group; PCOS (22%-29%) group; and PCOS (30%-37%) group. Hemodynamic, metabolic, and hormonal characteristics and HRV parameters were obtained before and after 16 weeks of APT. The PCOS (22%-29%) group exhibited lower vagal modulation than the CONTROL (22%-29%) group. In contrast, no significant differences were observed between the CONTROL (30%-37%) and PCOS (30%-37%) groups. Furthermore, the PCOS (30%-37%) group demonstrated lower sympathetic modulation than the PCOS (22%-29%) group. After APT, the PCOS (22%-29%) group increased in vagal modulation, while the PCOS (30%-37%) group increased in sympathetic modulation. PCOS affects vagal modulation; however, this effect may be masked at elevated levels of body fat. Additionally, the combination of excess body fat with endocrine-metabolic dysregulation appears to reduce sympathetic modulation, possibly due to sympathetic drive hyperactivity. APT positively affected HRV in both PCOS groups.

Blood volatile organic compounds as potential biomarkers for poly cystic ovarian syndrome (PCOS): An animal study in the PCOS rat model

Background:It is essential to determine the cut-off value of serum anti-Mullerian hormone (AMH) to predict the hyper response in assisted reproductive technology (ART). There are few studies mentioning the cut-off value for the hyper response in infertile women but not specifically for polycystic ovary syndrome (PCOS) and non-PCOS groups. With this in background, this study was conducted.Aim:To determine the cut-off value of serum AMH to predict the hyper response in women with PCOS and non-PCOS undergoing a controlled ovarian stimulation (COS) in ART.Objective:To compare the outcome of stimulation in PCOS and non-PCOS groups.Materials and Methods:All 246 women enrolled for Intra Cytoplasmic Sperm Injection (ICSI) fulfilling the selection criteria were recruited. On the day 3 of the cycle, the serum AMH, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), estradiol and antral follicle count (AFC) were measured. They underwent COS as per the unit protocol. They were divided into PCOS and non-PCOS groups as per the Rotterdam’s criteria. The mean age, duration of infertility, Body Mass Index (BMI), Ovarian reserve markers and outcome of stimulation were compared. Using the Statistical Package for the Social Sciences version 16.0 software, the significant difference was measured by multivariate analysis, as well as a one-way analysis of variance with Tukey’s post-hoc test was used.Results:Among 246 women, 31.3% were in PCOS group, and 68.7% were in non-PCOS group. Comparison of PCOS and non-PCOS groups showed a significant difference in the age with the mean age being 29.2 and 31.5 years, respectively. The mean AMH and AFC were 2-fold higher in PCOS group. The mean number of follicles, oocytes retrieved, MII and oocytes fertilised were significantly higher in PCOS group. The pregnancy rate was 52.6% in PCOS and 30.9% in non-PCOS group. In the PCOS group, 22.1% had ovarian hyper stimulation syndrome (OHSS), and only 4.7% had OHSS in non-PCOS group (P = 0.0005). Receiving Operator Curve (ROC) curve was plotted to predict the hyper response, which showed a cut-off value of 6.85 ng/ml with a sensitivity of 66.7% and a specificity of 68.7% for PCOS group and 4.85 ng/ml with a sensitivity of 85.7% and a specificity of 89.7% in non-PCOS group.Conclusion:The cut-off value of serum AMH to predict the hyper response in PCOS group is 6.85 ng/ml and in non-PCOS group is 4.85 ng/ml.