scholarly journals C/EBP-β and SIRT1 regulate IL-18 expression in the proliferative phase endometrium of patients with polycystic ovary syndrome (PCOS)

2020 ◽  
Author(s):  
Xiaoyu Long ◽  
Honghao Wang ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Luciferase Assay ◽  
Control Group ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Search Tool ◽  
Proliferative Endometrium

Abstract Background：Previous studies have shown that patients with polycystic ovary syndrome (PCOS) tend to suffer from low-grade chronic inflammation. Besides, our previous studies have confirmed that IL-18 is highly expressed in the serum and endometrium of patients with PCOS. Nevertheless, the mechanism underlying IL-18 elevation remains unclear. The aim of this study was to explore the signaling pathways that lead to the up-regulation of IL-18 in the endometrium of PCOS patients. Materials and Methods: By using the TF-Search tool, we predicted that C/EBP-β might be a transcription factor of IL-18, and deacetylase SIRT1 might be involved in its regulation. Consequently, SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients and control groups were analyzed using immunohistochemistry, real-time quantitative PCR and Western Blot; the diagnosis of PCOS was based on the 2003 Rotterdam ESHRE/ASRM criteria. The interaction between C/EBP-β and IL-18 was verified by double luciferase assay. Results: The gene and protein levels of SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients were significantly higher compared to the control group. Immunohistochemical experiments confirmed that SIRT1 was mainly expressed in the endometrial nucleus, while C/EBP-β was mainly expressed in the endometrial nucleus and cytoplasm. The interaction between C/EBP-β and IL-18 was confirmed by double luciferase assay. Conclusion: SIRT1 and C/EBP-β are highly expressed in the endometrium of PCOS patients, and may participate in the regulation of IL-18. These results further our understanding of the role of C/EBP-β in PCOS and may be used as a basis for the development of targeted therapies for this disease.

scholarly journals C/EBP-β and SIRT1 regulate IL-18 expression in the proliferative phase endometrium of patients with polycystic ovary syndrome (PCOS)

2020 ◽  
Author(s):  
Xiaoyu Long ◽  
Honghao Wang ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Luciferase Assay ◽  
Control Group ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Search Tool ◽  
Proliferative Endometrium

Abstract Background：Previous studies have shown that patients with polycystic ovary syndrome (PCOS) tend to suffer from low-grade chronic inflammation. Besides, our previous studies have confirmed that IL-18 is highly expressed in the serum and endometrium of patients with PCOS. Nevertheless, the mechanism underlying IL-18 elevation remains unclear. The aim of this study was to explore the signaling pathways that lead to the up-regulation of IL-18 in the endometrium of PCOS patients. Materials and Methods: By using the TF-Search tool, we predicted that C/EBP-β might be a transcription factor of IL-18, and deacetylase SIRT1 might be involved in its regulation. Consequently, SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients and control groups were analyzed using immunohistochemistry, real-time quantitative PCR and Western Blot; the diagnosis of PCOS was based on the 2003 Rotterdam ESHRE/ASRM criteria. The interaction between C/EBP-β and IL-18 was verified by double luciferase assay. Results: The gene and protein levels of SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients were significantly higher compared to the control group. Immunohistochemical experiments confirmed that SIRT1 was mainly expressed in the endometrial nucleus, while C/EBP-β was mainly expressed in the endometrial nucleus and cytoplasm. The interaction between C/EBP-β and IL-18 was confirmed by double luciferase assay. Conclusion: SIRT1 and C/EBP-β are highly expressed in the endometrium of PCOS patients, and may participate in the regulation of IL-18. These results further our understanding of the role of C/EBP-β in PCOS and may be used as a basis for the development of targeted therapies for this disease.

scholarly journals C/EBP-β and SIRT1 regulate IL-18 expression in the proliferative phase endometrium of patients with polycystic ovary syndrome (PCOS)

2019 ◽  
Author(s):  
Xiaoyu Long ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang ◽  
Jie Qiao
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Luciferase Assay ◽  
Control Group ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Proliferative Endometrium ◽  
And Control

Abstract Background：Previous studies have shown that patients with polycystic ovary syndrome present with low-grade chronic inflammation. Our previous studies have confirmed that IL-18 is highly expressed in the serum and endometrium of patients with polycystic ovary syndrome. However, the mechanism of IL-18 elevation remains unclear. Therefore, this study aims to explore the signaling pathways that lead to the up-regulation of IL-18 in endometrium of PCOS patients. We predicted that C/EBP-β might be a transcription factor of IL-18 by using TF-Search tool, and deacetylase SIRT1 might be involved in its regulation. Method：SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients and control group by immunohistochemical method.The expression was localized. The genes and proteins of SIRT1 and C/EBP-β in endometrium of PCOS and control group were detected by real-time quantitative PCR and Western Blot respectively. The interaction between C/EBP-β and IL-18 was verified by double luciferase assay. Result(s): The gene and protein levels of SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients were significantly higher than those of the control group. Immunohistochemical experiments confirmed that SIRT1 was mainly expressed in endometrial nucleus, while C/EBP-β was mainly expressed in endometrial nucleus and cytoplasm. The interaction between C/EBP-β and IL-18 was confirmed by double luciferase assay. Conclusion: SIRT1 and C/EBP-β are highly expressed in endometrium of PCOS patients, and may play a role in the regulation of IL-18.

scholarly journals C/EBP-β and SIRT1 regulate IL-18 expression in the proliferative phase endometrium of patients with polycystic ovary syndrome (PCOS)

2020 ◽  
Author(s):  
Xiaoyu Long ◽  
Honghao Wang ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang(New Corresponding Author) ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Luciferase Assay ◽  
Control Group ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Real Time Quantitative Pcr ◽  
Protein Levels ◽  
Proliferative Endometrium ◽  
And Control

Abstract Background：Previous studies have shown that patients with polycystic ovary syndrome present with low-grade chronic inflammation. Our previous studies have confirmed that IL-18 is highly expressed in the serum and endometrium of patients with polycystic ovary syndrome. However, the mechanism of IL-18 elevation remains unclear. Therefore, this study aims to explore the signaling pathways that lead to the up-regulation of IL-18 in endometrium of PCOS patients. We predicted that C/EBP-β might be a transcription factor of IL-18 by using TF-Search tool, and deacetylase SIRT1 might be involved in its regulation. Method：SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients and control group by immunohistochemical method.The expression was localized. The genes and proteins of SIRT1 and C/EBP-β in endometrium of PCOS and control group were detected by real-time quantitative PCR and Western Blot respectively. The interaction between C/EBP-β and IL-18 was verified by double luciferase assay. Result(s): The gene and protein levels of SIRT1 and C/EBP-β in proliferative endometrium of PCOS patients were significantly higher than those of the control group. Immunohistochemical experiments confirmed that SIRT1 was mainly expressed in endometrial nucleus, while C/EBP-β was mainly expressed in endometrial nucleus and cytoplasm. The interaction between C/EBP-β and IL-18 was confirmed by double luciferase assay. Conclusion: SIRT1 and C/EBP-β are highly expressed in endometrium of PCOS patients, and may play a role in the regulation of IL-18.

Abnormal expression of uncoupling protein-2 correlates with CYP11A1 expression in polycystic ovary syndrome

2011 ◽  
Vol 23 (4) ◽  
pp. 520 ◽  
Author(s):  
Yun Liu ◽  
Hong Jiang ◽  
Ling-Yun He ◽  
Wu-Jian Huang ◽  
Xiao-Yu He ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Early Stage ◽  
Uncoupling Protein ◽  
Serum Insulin ◽  
Ovarian Tissue ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Ovary Syndrome ◽  
Protein Levels

Polycystic ovary syndrome (PCOS) may result from hypersensitivity to insulin, which is negatively regulated by uncoupling protein (UCP)-2. Because cholesterol side-chain cleavage enzyme (CYP11A1) is closely linked to PCOS, the expression of UCP-2 and CYP11A1 in ovarian tissues from PCOS patients was examined in the present study. Twelve PCOS patients with hyperandrogenaemia who underwent laparoscopic ovarian wedge resection and 12 age-matched control patients who underwent contralateral ovarian biopsy were enrolled in the study. UCP-2 expression in early stage (primordial, primary and secondary) and late stage (sinus and mature) follicles was examined using immunohistochemistry, whereas UCP-2 and CYP11A1 mRNA and protein levels in ovarian tissue were determined using quantitative reverse transcription–polymerase chain reaction and western blot analyses, respectively. UCP-2 expression increased significantly with follicular development in both control and PCOS tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls. In addition, both UCP-2 and CYP11A1mRNA and protein levels, mean fasting blood glucose concentrations and fasting serum insulin levels were significantly higher in PCOS patients compared with the control group. Finally, a significant correlation between UCP-2 and CYP11A1 expression was found in PCOS but not control patients. In conclusion, in PCOS patients, there was a correlation between UCP-2 and CYP11A1 expression, which was significantly higher than in the control group. These changes in UCP-2 and CYP11A1 expression may mediate follicle development in PCOS.

scholarly journals Telomere Length Differently Associated to Obesity and Hyperandrogenism in Women With Polycystic Ovary Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Mariela Edith Velazquez ◽  
Andrea L. Millan ◽  
Mailén Rojo ◽  
Giselle Adriana Abruzzese ◽  
Silvina Ema Cocucci ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Telomere Length ◽  
Polycystic Ovary ◽  
Major Effect ◽  
Control Group ◽  
Unrelated Donor ◽  
Ovary Syndrome ◽  
Blood Leukocytes ◽  
Real Time Quantitative Pcr ◽  
Pcos Group

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.

scholarly journals The Effect of Glutamine on Dehydroepiandrosterone-Induced Polycystic Ovary Syndrome Rats

2020 ◽  
Author(s):  
Gengxiang Wu ◽  
Xue Hu ◽  
Jinli Ding ◽  
Jing Yang
Keyword(s):  
Oxidative Stress ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Antioxidant Properties ◽  
Stress Factors ◽  
Control Group ◽  
Low Grade ◽  
Ovary Syndrome ◽  
Pcos Group ◽  
And Oxidative Stress

Abstract Background Previous studies have shown that chronic inflammation and oxidative stress may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS), and glutamine (Gln) showed the anti-inflammatory and antioxidant properties. So the aim of this study is to investigate the effect of glutamine supplementation on PCOS rats. Methods Female Sprague–Dawley rats were randomly assigned into five groups (n = 10 /group), control group, PCOS group, PCOS+0.5g/kg Gln group, PCOS+0.75g/kg Gln group and PCOS+1.0g/kg Gln group. All the PCOS rats were administrated with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 consecutive days, all the PCOS+Gln groups were intraperitoneal injected Gln twice in the next morning after the last DHEA injection. All the samples were collected 12 hours after the last administration. Ovarian histological examinations were analyzed and the concentration of serum hormone, inflammatory and oxidative stress factors were measured. Results There was no obvious ovarian histological change among the PCOS group and PCOS+Gln groups. All the detected inflammation factors (IL-6, IL-18, TNF-α and CRP) showed significantly higher in all the PCOS groups compared to the control group (P<0.01), and were significantly decreased with the low supplementation of glutamine (P<0.01, include 0.5g/kg group and 0.75g/kg group).Concentrations of SOD were significantly lower in all the PCOS groups (P<0.01) compared to the control group, and increased significantly with the low supplementation of glutamine (P<0.01, include 0.5g/kg group and 0.75g/kg group). Serum concentrations of MDA, NO and NOS were significantly higher in PCOS group (P<0.01) compared with the control group, and significantly decreased to the comparative levels of control group with the low supplementation of glutamine (P<0.01, include 0.5g/kg group and 0.75g/kg group). Conclusion There is low-grade inflammation and oxidative stress in DHEA-induced PCOS rats. The supplementation of glutamine with doses of 0.5g/kg and 0.75g/kg could effectively ameliorate the inflammatory and oxidative stress conditions of PCOS.

scholarly journals Urinary bisphenol A in women with polycystic ovary syndrome – a possible suppressive effect on steroidogenesis?

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Bisphenol A ◽  
Steroid Hormones ◽  
Polycystic Ovary ◽  
Suppressive Effect ◽  
Human Reproduction ◽  
Control Group ◽  
Ovary Syndrome ◽  
Ovarian Steroidogenesis ◽  
The Relationship

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.

scholarly journals The Relevant Hormonal Levels and Diagnostic Features of Polycystic Ovary Syndrome in Adolescents

2020 ◽  
Vol 9 (6) ◽  
pp. 1831
Author(s):  
Elena Khashchenko ◽  
Elena Uvarova ◽  
Mikhail Vysokikh ◽  
Tatyana Ivanets ◽  
Lyubov Krechetova ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Polycystic Ovary Syndrome ◽  
Diagnostic Accuracy ◽  
Polycystic Ovary ◽  
Regression Function ◽  
High Sensitivity ◽  
Sex Hormone Binding Globulin ◽  
Control Group ◽  
Ovary Syndrome ◽  
Diagnostic Features

Relevance: The clinical picture of polycystic ovary syndrome (PCOS) is extremely polymorphic, especially in adolescence. At the same time, the diagnostic criteria of PCOS in adolescence are still under discussion, and the hormonal parameters, including anti-Mullerian hormone range and hyperandrogenism, are not determined. The aim of the present study was to characterize the pivotal clinical and hormonal features of PCOS in adolescents and to establish the age-specific thresholds of the most essential hormonal parameters. Design: A case-control study. Methods: The study included 130 girls with PCOS according to the complete Rotterdam criteria, aged 15 to 17 years. The control group consisted of 30 healthy girls with a regular menstrual cycle of the same age. A complete clinical and laboratory examination, hormonal assays, and ultrasound of the pelvic organs were performed. The serums anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), LH/FSH, prolactin, estradiol, 17α-OH progesterone (17α-OHP), androstenedione, testosterone (T), dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), leptin, and free androgen index (FAI) were analyzed. The diagnostic accuracy of AMH, FAI, LH/FSH, T, and androstenedione levels in predicting PCOS in adolescents was established using a logistic regression model and calculating area under the receiver operator characteristic (ROC) curve (AUC). Results: The serum levels of LH (9.0 (5.4–13.8) vs. 3.7 (2.5–4.7) IU/L; p < 0.0001), LH/FSH (1.6 (1.0–2.3) vs. 0.7 (0.5–1.1); p < 0.0001), 17α–OHP (4.1 (3.2–5.1) vs. 3.4 (2.7–3.8) nmol/L; p = 0.0071), cortisol (464.0 ± 147.6 vs. 284.0 ± 129.7 nmol/L; p < 0.0001), prolactin (266.0 (175.0–405.0) vs. 189.0 (142.0–269.0) mIU/L; p = 0.0141), T (1.9 (1.2–2.5) vs. 0.8 (0.7–1.1) nmol/L; p < 0.0001), androstenedione (15.8 (11.6–23.2) vs. 8.3 (6.5–10.8) ng/mL; p < 0.0001), AMH (9.5 (7.5–14.9) vs. 5.8 (3.8–6.9) ng/mL; p < 0.0001), FAI (5.5 (2.8–7.0) vs. 1.6 (1.1–2.3); p < 0.0001), SHBG (37.0 (24.7–55.5) vs. 52.9 (39.0–67.6) nmol/L; p = 0.0136), DHEAS (6.8 ± 3.2 vs. 5.1 ± 1.5 μmol/L; p = 0.0039), and leptin (38.7 ± 27.1 vs. 23.7 ± 14.0 ng/mL; p = 0.0178) were significantly altered in the PCOS patients compared to the controls. Multivariate analysis of all studied hormonal and instrumental parameters of PCOS in adolescents revealed as the most essential: AMH level > 7.20 ng/mL, FAI > 2.75, androstenedione > 11.45 ng/mL, total T > 1.15 nmol/L, LH/FSH ratio > 1.23, and the volume of each ovary > 10.70 cm3 (for each criterion sensitivity ≥ 75.0–93.0%, specificity ≥ 83.0–93.0%). The diagnostic accuracy of PCOS determination was 90.2–91.6% with the combined use of either four detected indexes, which was significantly higher than the use of each index separately. The accuracy of PCOS diagnostics reached 92% using AMH and leptin concentrations when the value of the logistic regression function [85.73 − (1.73 × AMH) − (0.12 × Leptin)] was less than 70.72. Conclusions: The results of the study estimate the threshold for AMH, FAI, androstenedione, testosterone, LH/FSH, and ovarian volume, which could be suggested for use in the PCOS diagnostics in adolescents with a high sensitivity and specificity. Moreover, the combination of either four determined indexes improved the diagnostic accuracy for the PCOS detection in adolescents.

Health Care-Related Economic Burden of Polycystic Ovary Syndrome in the United States: Pregnancy-Related and Long-Term Health Consequences

2021 ◽  
Author(s):  
Carrie Riestenberg ◽  
Anika Jagasia ◽  
Daniela Markovic ◽  
Richard P Buyalos ◽  
Ricardo Azziz
Keyword(s):  
United States ◽  
Polycystic Ovary Syndrome ◽  
Economic Burden ◽  
Polycystic Ovary ◽  
The United States ◽  
Reproductive Age ◽  
Cochrane Library ◽  
Control Group ◽  
Ovary Syndrome

Abstract Context Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive-aged women, affecting approximately 5-20% of women of reproductive age. A previous estimate noted that the economic burden of PCOS approximates $3.7 billion annually in 2020 USD when considering only the costs of the initial diagnosis and of reproductive endocrine morbidities, not considering the costs of pregnancy-related and long-term morbidities. Objective To estimate the excess prevalence and economic burden of pregnancy-related and long-term health morbidities attributable to PCOS. Data Sources PubMed, EmBase and Cochrane Library. Study Selection Studies in which the diagnosis of PCOS was consistent with the Rotterdam, National Institutes of Health (NIH), or Androgen Excess & PCOS (AE-PCOS) Society criteria, or that used electronic medical record diagnosis codes, or diagnosis based on histopathologic sampling were eligible for inclusion. Studies that included an outcome of interest and a control group of non-PCOS patients who were matched or controlled for body mass index (BMI) were included. Data Extraction Two investigators working independently extracted data on study characteristics and outcomes. Data Synthesis Data was pooled using random-effects meta-analysis. The I 2statistic was used to assess inter-study heterogeneity. The quality of selected studies was assessed using the Newcastle-Ottawa Scale. Results The additional total healthcare-related economic burden due to pregnancy-related and long-term morbidities associated with PCOS in the United States is estimated to be $4.3 billion annually in 2020 USD. Conclusions Together with our prior analysis, the economic burden of PCOS is estimated at $8 billion annually in 2020 USD.

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