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

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 ◽  
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.


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.


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.


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.


2019 ◽  
Author(s):  
Christian Obirikorang ◽  
William K.B.A. Owiredu ◽  
Sandra Adu-Afram ◽  
Emmanuel Acheampong ◽  
Evans Adu Asamoah ◽  
...  

Abstract Objectives: To assess variability and predictability of adiponectin, leptin, resistin and their ratios in non-obese and obese women with anovulatory polycystic ovary syndrome (aPCOS). Results: A total of 52 ovulatory controls (mean age=31.63±4.88 years, BMI=25.33±2.68 kg/m3); 54 non-obese [mean age=32.11±4.25 years, BMI=25.72±2.95 kg/m3] and 50 obese women with aPCOS [mean age= 33.64±4.14 years, BMI=39.19±2.99 kg/m3] were recruited. The aPCOS group had lower adiponectin [13.0(10.49-16.59) vs 18.42(15.72-19.92) µg/ml, p<0.0001], adiponectin: leptin ratio (A:L) [0.60(0.35-0.88) vs 1.19(0.92-1.37), p<0.0001], and adiponectin: resistin ratio (A:R) [0.30(0.21-0.43) vs 0.42(0.32-0.62), p<0.0001] but a higher leptin [20.02(14.54-26.80) vs 16.17(14.51-18.36) ng/ml, p<0.0001] and leptin: resistin ratio (L:R) [0.53(0.37-0.82) vs 0.40(0.27-0.48), p<0.0001] compared to the controls. The obese aPCOS group had lower adiponectin [11.04(5.66-13.25) vs 14.18(11.04-18.02), p<0.0001 and 18.42(15.72-19.92) µg/ml, p<0.0001], A:L [0.36(0.27-0.44) vs 0.78(0.61-1.16), p<0.0001 and 1.19(0.92-1.37), p<0.0001], and A:R [0.24(0.17-0.38) vs 0.40(0.23-0.58), p<0.0001 and 0.42(0.32-0.62), p<0.0001] but a higher leptin [26.80(14.28-32.09) vs 17.95(14.86-21.26), p<0.05 and 16.17(14.51-18.36) ng/ml, p<0.0001] and L:R [0.63(0.46-1.03) vs 0.41(0.30-0.61), p<0.0001 and 0.40(0.27-0.48), p<0.0001] compared to the non-obese aPCOS and control group, respectively. A:L showed the best discriminatory power in predicting aPCOS (AUC=0.83), followed by adiponectin alone (AUC=0.79), L:R and leptin alone (both AUC=0.69). Resistin alone had the poorest discriminatory power (AUC=0.48).


2019 ◽  
Vol 01 (04) ◽  
pp. 149-153
Author(s):  
Uki Retno Budihastuti ◽  
Eriana Melinawati ◽  
Sri Sulistyowati ◽  
Abdurrahman Laqief ◽  
M. Firdinan Dekawan

Objective: The study was conducted to determine whether there were differences in COX-2 expression in endometrial women with PCOS compared to fertile women. Methods: This study is a case-control study investigating the relationship between exposure (research factors) and disease, by comparing case group and control group based on their exposure status. The samples of this study were infertile polycystic ovary syndrome patients who were treated at the Sekar Fertility Clinic in Dr. Moewardi Hospital Surakarta, and fertile women seeking treatment at Dr. Moewardi Hospital Surakarta. The number of samples were 60 subjects consisting of 30 PCOS patients and 30 fertile women. The expression of COX-2 in endometrial biopsy LH + 5 until LH + 10 which meet the inclusion with Rotterdam criteria and exclusion criteria was checked by immunohistochemistry. The data was analyzed using the Mann-Whitney test. Results: The mean COX-2 expression in PCOS (10.83 ± 5.35) in fertile women (37.00 ± 7.76), p = 0.005. Regression test of COX-2 by adjusting external variables (occupation, age, education, menstrual disorders, familial history, menstrual cycle, menarche, obesity, contraception history) shows also higher expression in PCOS patient with OR = -7.063; CI = 0.462–108.066; p = 0.160. Conclusion: COX-2 expression in endometrium of women with PCOS is lower than it is in fertile women.


2006 ◽  
Vol 154 (6) ◽  
pp. 883-890 ◽  
Author(s):  
A Dagre ◽  
J Lekakis ◽  
C Mihas ◽  
A Protogerou ◽  
L Thalassinou ◽  
...  

Objective: The aim of this study was to assess non-invasively endothelial function of young women with polycystic ovary syndrome (PCOS) in comparison with healthy age-matched women and a group of young women with idiopathic hirsutism (IH). The possible role of metabolic and hormonal parameters on endothelial function was also examined. Design: Descriptive clinical trial. Methods: Fifty-six women, 27 with PCOS, 16 with IH and 13 healthy age-matched women were studied. Endothelial function of resistance arteries was assessed by venous occlusion plethysmography. Metabolic and hormonal parameters were estimated in this study population. Results: The duration of reactive hyperemia (durRH) was shorter in PCOS group when compared with normal controls (63.75 ± 13.33 s vs 113.18 ± 20.92 s, P = 0.036). A similar finding was observed when PCOS were compared with IH group (63.75 ± 13.33 s vs 105 ± 17.20 s, P = 0.05). The durRH did not differ between IH and control group (105 ± 17.20 s vs 113.18 ± 20.92 s, ns). A significant positive linear correlation was found between the durRH and dehydroepiandrosterone-sulfate (DHEA-S) levels (r = +0.48, P = 0.04) in the PCOS group. The basal insulin resistance index (HOMA) differed significantly between PCOS, IH and control groups. There was no significant correlation between durRH and HOMA index or testosterone levels in the PCOS group. Conclusions: Endothelial dysfunction may be an early sign of cardiovascular system abnormalities in young PCOS women. It is possible that increased DHEA-S levels may offer a cardioprotective advantage that attenuates the effects of cardiovascular risk factors that accompany PCOS.


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