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 ◽  
...  

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.

2019 ◽  
Author(s):  
Xiaoyu Long ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang ◽  
Jie Qiao

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.


2020 ◽  
Author(s):  
Xiaoyu Long ◽  
Honghao Wang ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang(New Corresponding Author) ◽  
...  

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.


2020 ◽  
Author(s):  
Xiaoyu Long ◽  
Honghao Wang ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hongliang Li ◽  
Yankai Guo ◽  
Gege Zhang ◽  
Jielin Deng ◽  
Hayley Fischer ◽  
...  

Abstract Background: Polycystic ovary syndrome (PCOS), a metabolic and reproductive associated disease, defined as hyperandrogenism with reproductive dysfunction including menstrual disorder, anovulation, infertility, polycystic ovary and so on. We previously showed reported a high percentage of activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR) in PCOS patients, and further demonstrated elevated GnRHR-autoantibody (GnRHR-AAb) could induced insulin resistance in energy storage and peripheral tissue in immunized animals. In the present study, we have now induced specific GnRHR-ECL2 AAb in rats and explored the underlying mechanisms of their resultant reproductive dysfunction. Methods: Sixteen SD rats were randomly divided into 2 groups: a GnRHR group (n=8) and a control group (n=8). Rats in the GnRHR group were immunized with GnRHR ECL2 peptide while the controls were not. Epitope mapping of GnRHR-ECL2-directed AAb was performed using octapeptide multipin solid-phase peptides. Rat estrus cycle was measured through pudendum appearance and vaginal smears. Ovarian and pituitary tissues were collected to observe ovarian morphological changes, to examine the expressions of proteins and genes of insulin signaling pathway by Quantitative real-time PCR respectively. The concentration of inflammatory cytokines in the ovary was detected by Bio-plex Pro™ magnetic bead-based assays on the Bio-plex®. Results: The GnRHR-AAb titers and activity in the GnRHR group were significantly higher than the control group, and the GnRHR-AAb from the immunized rats reacted predominantly with the peptide sequence FSQCVTHC of the GnRHR-ECL2. Numbers of LH pulses and concentration of testosterone in GnRHR group were significantly higher than control group. The GnRHR group exhibited lower frequency of in the appearance of proestrus and estrous phases while the control group represented had a higher frequency in the appearance of metestrus and diestrus stages on estrus cyclicity. The GnRHR-immunized group showed demonstrated increased atretic follicles, decreased corpora lutea, loosely packed granulosa cells, and thecal cell hyperplasia in ovarian tissue compared with controls group. There was GnRHR group represented increased expressions of IRS-1, PI3K and GLUT-1 in ovarian and pituitary tissues compared with control group. However, no obvious changes of inflammatory cytokines are observed in ovarian tissues between two groups. Conclusion: Chronic elevated GnRHR-AAb exerts induced reproductive dysfunction through increased ovarian LH secretion and androgen production, thus likely leading to compensatory hyperinsulinemia which ultimately enhanced insulin signaling in reproductive tissues to exert more and androgen production to, which may provide a novel etiological mechanism for PCOS.


2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Ning Zhang ◽  
Chang Li ◽  
Ying Guo ◽  
Hai-cui Wu

Objective. This was a population-based cohort study, to compare the type and structure of intestinal flora in patients with polycystic ovary syndrome (PCOS) with phlegm-dampness syndrome, nonphlegm-dampness syndrome, and normal population. Besides, changes in the intestinal flora and the clinical curative effects of Jiawei Qi Gong Wan on phlegm-dampness syndrome in patients with polycystic ovary syndrome (PCOS) were evaluated. Patients and Methods. A total of 22 patients with PCOS with phlegm-dampness syndrome, 21 PCOS patients with nonphlegm-dampness syndrome, and 20 control volunteers were selected for this study. The general index, sex hormone index, fasting blood glucose (FPG), and serum fasting insulin (FINS) were determined in each of the groups. The intestinal flora of each group was determined by the 16s rDNA high-throughput sequencing technique. Besides, the PCOS with phlegm-dampness syndrome group was treated with Jiawei Qi Gong Wan, and the changes in TCM syndrome, sex hormone index, BMI, WHR, FPG, FINS, HOMA-IR, and intestinal flora were determined before and after treatment. Results. PCOS patients with phlegm-dampness syndrome showed characteristics of obesity and insulin resistance. There were several differences in both structure and function of the intestinal flora between PCOS patients with phlegm-dampness syndrome, PCOS patients with nonphlegm-dampness syndrome, and the control group. An imbalance in the intestinal flora may be a key factor in the pathogenesis of PCOS with phlegm-dampness syndrome and also has a specific influence on glucose and lipid metabolism, obesity, and the menstrual cycle in PCOS patients with phlegm-dampness syndrome. Besides, the imbalance is associated with a decrease in the number of butyrate-producing bacteria, an increase in the number of lipopolysaccharide-producing bacteria, and an increase in proinflammatory bacteria. The intestinal flora in PCOS patients with phlegm-dampness syndrome was found to be linked to obesity, impaired glucose tolerance, and hyperandrogenemia. Treatment with Jiawei Qi Gong Wan was found to increase the diversity of intestinal flora, increase the number of intestinal probiotics, and improve the structure and functional genes of intestinal flora which improved the state of insulin resistance, regulated endocrine metabolism, and improved the overall symptoms. Conclusions. Intestinal flora imbalance is a key factor in the pathogenesis of PCOS with phlegm-dampness syndrome. Besides, Jiawei Qi Gong Wan improves insulin resistance which is linked to the status of the intestinal flora in PCOS patients with phlegm-dampness syndrome.


2020 ◽  
Author(s):  
Xiaoyu Long ◽  
Honghao Wang ◽  
Xiaohui Zhu ◽  
Rong Li ◽  
Yan Yang ◽  
...  

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.


2017 ◽  
Vol 66 (6) ◽  
pp. 73-80 ◽  
Author(s):  
Maria I. Yarmolinskaya ◽  
Nigar F. Ganbarli ◽  
Natalia N. Tkachenko ◽  
Vera I. Nikolaeva ◽  
Gulrukhsor Kh. Tolibova ◽  
...  

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age. It is known that kisspeptin stimulates activity of GnRH neurons and secretion of FSH and LH, thus disruption of interaction between kisspeptin and its receptor leads to anovulation. The aim of the study was to investigate the role kisspeptin in the pathogenesis of polycystic ovary syndrome. Materials and methods. The study included 14 patients with classic phenotype of PCOS and 11 healthy women of the control group. All the patients underwent laparoscopy and hysteroscopy with histological examination of ovarian tissue and endometrium. Determination of kisspeptin, FSH, LH, prolactin, AMH, estradiol, estrone, androgens (free testosterone and dehydroepiandrosterone sulfate) levels in peripheral blood in healthy women and patients with PCOS was performed by ELISA on the 2d and 8th days of menstrual cycle. Progesterone levels were investigated on the 18th-22d days of menstrual cycle. Expression of kisspeptin and its receptor in ovarian tissue and endometrium was estimated using immunohistochemical method. Results. Level of kisspeptin in peripheral blood of patients with PCOS tends to increase compared to its level in the control group, but the found difference was not reliable. Direct correlation between serum level of kisspeptin and levels of LH, free testosterone and DHEA-S was revealed in patients with PCOS. Immunohistochemical study in patients with PCOS showed a significant increase in the area of expression of КІЅЅ1 and KISS1R receptor in endometrium and in ovarian biopsies compared to these values in the control group. Conclusion. The obtained data show a definite role of kisspeptin in pathogenesis of polycystic ovary syndrome, but further research is needed.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Juan Du ◽  
Xiangyan Ruan ◽  
Fengyu Jin ◽  
Yanglu Li ◽  
Jiaojiao Cheng ◽  
...  

Abstract Purpose To investigate abnormalities of early folliculogenesis and Anti-Müllerian hormone (AMH) concentrations in polycystic ovary syndrome (PCOS) patients, and to analyze the association between AMH and early-stage follicle densities (FD). Methods A total of 175 patients underwent ovarian tissue cryopreservation in the first official cryobank in China, of which 16 patients aged 30–40 years old were diagnosed with endometrial cancer (all without initial chemo/radiotherapy), including 5 patients with concurrent PCOS and the other 11 patients without. We obtained standard cortical biopsies to measure FD using calcein staining. Blood samples were collected before cryopreservation to evaluate AMH concentrations. Results PCOS showed nearly three times the primordial and primary FD than NPCOS (P = 0.027), as well as more secondary preantral follicles (P = 0.002). A significantly higher proportion of secondary preantral follicles and a lower proportion of primordial and primary follicles were observed in PCOS (P = 0.01). Furthermore, the AMH concentration in PCOS was four times higher than that in NPCOS (P = 0.003), which is significantly correlated with primordial and primary follicle densities (r = 0.855, P < 0.001) and secondary preantral follicle densities (r = 0.732, P = 0.007). Conclusions We found significant disorders of early folliculogenesis in PCOS, which showed close correlation with increased AMH concentrations. To our knowledge, abnormalities of early-stage follicles have been shown for the first time in ovarian tissue of Chinese PCOS women. We suppose that the elevated AMH level is associated with abnormalities of early folliculogenesis within the complex PCOS pathogenesis, which may explain why AMH has the potential to be used as a biomarker for the diagnosis of PCOS. Our findings provide more implications for understanding the mechanism of PCOS, and new directions for further studies.


Author(s):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová

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.


2021 ◽  
Vol 49 (7) ◽  
pp. 030006052110317
Author(s):  
Chenyun Miao ◽  
Qingge Guo ◽  
Xiaojie Fang ◽  
Yun Chen ◽  
Ying Zhao ◽  
...  

Objective This meta-analysis evaluated the effect of probiotics and synbiotics on insulin resistance in patients with polycystic ovary syndrome (PCOS). Methods A systematic search was performed to identify all relevant publications listed on the electronic databases (PubMed®, Web of Science, Embase® and China National Knowledge Infrastructure) between inception and 30 October 2020. All statistical analyses were performed on randomized controlled trials (RCTs) using RevMan version 5.3 software provided by the Cochrane Collaboration. Results A total of 486 patients from seven RCTs were included in the meta-analysis. Probiotic and synbiotic supplementation appeared to improve levels of homeostatic model assessment of insulin resistance (mean difference = –0.37; 95% confidence interval –0.69, –0.05) and serum insulin (standardized mean difference = –0.66; 95% confidence interval –1.19, –0.12). The results failed to show any influence of probiotic and synbiotic supplementation on body mass index, waist circumference, hip circumference and fasting blood sugar. Conclusions Probiotics and synbiotics appear to have a partially beneficial effect on indices of insulin resistance in patients with PCOS.


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