scholarly journals Follicular hyperandrogenism downregulates aromatase in luteinized granulosa cells in polycystic ovary syndrome women

Reproduction ◽  
2015 ◽  
Vol 150 (4) ◽  
pp. 289-296 ◽  
Author(s):  
Fang Yang ◽  
Ye-Chun Ruan ◽  
Yun-jie Yang ◽  
Kai Wang ◽  
Shan-shan Liang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Inhibitory Effect ◽  
Reproductive Technology ◽  
Ovary Syndrome ◽  
Protein Levels ◽  
Androgen Receptor Antagonist ◽  
And Control

Women with polycystic ovary syndrome (PCOS) undergoing IVF–embryo transfer based-assisted reproductive technology (ART) treatment show variable ovarian responses to exogenous FSH administration. For better understanding and control of PCOS ovarian responses in ART, the present study was carried out to compare the follicular hormones and the expression of granulosa cell genes between PCOS and non-PCOS women during ART treatment as well as their IVF outcomes. Overall, 138 PCOS and 78 non-PCOS women were recruited for the present study. Follicular fluid collected from PCOS women showed high levels of testosterone. The expression of aromatase was found significantly reduced in luteinized granulosa cells from PCOS women. In cultured luteinized granulosa cells isolated from non-PCOS women, their exposure to testosterone at a level that was observed in PCOS follicles could decrease both mRNA and protein levels of aromatase in vitro. The inhibitory effect of testosterone was abolished by androgen receptor antagonist, flutamide. These results suggest that the hyperandrogenic follicular environment may be a key hazardous factor leading to the down-regulation of aromatase in PCOS.

scholarly journals Circadian Clock Genes REV-ERBs Inhibits Granulosa Cells Apoptosis by Regulating Mitochondrial Biogenesis and Autophagy in Polycystic Ovary Syndrome

2021 ◽  
Vol 9 ◽  
Author(s):  
Lihua Sun ◽  
Hui Tian ◽  
Songguo Xue ◽  
Hongjuan Ye ◽  
Xue Xue ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Circadian Clock ◽  
Granulosa Cells ◽  
Clock Genes ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Ovary Syndrome ◽  
Circadian Clock Genes ◽  
Mitochondrial Biosynthesis

Polycystic ovary syndrome (PCOS) is an endocrinopathy with complex pathophysiology that is a common cause of anovulatory infertility in women. Although the disruption of circadian rhythms is indicated in PCOS, the role of the clock in the etiology of these pathologies has yet to be appreciated. The nuclear receptors REV-ERBα and REV-ERBβ are core modulators of the circadian clock and participate in the regulation of a diverse set of biological functions. However, in PCOS, the expression of REV-ERBs and their effects remain unclear. Here, we demonstrate that the levels of REV-ERBα and REV-ERBβ expression were lower in the granulosa cells of PCOS patients than in control subjects. In vitro, we found that the overexpression of REV-ERBα and REV-ERBβ, and their agonist SR9009, promoted the expression of mitochondrial biosynthesis genes PGC-1α, NRF1, and TFAM and inhibited autophagy in KGN cells. Our results also indicate that REV-ERBα and REV-ERBβ can inhibit apoptosis in granulosa cells and promote proliferation. Importantly, the REV-ERB agonist SR9009 ameliorates abnormal follicular development by promoting mitochondrial biosynthesis and inhibiting autophagy in a mouse PCOS model. This allows us to speculate that SR9009 has potential as a therapeutic agent for the treatment of PCOS.

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.

scholarly journals Chemerin regulates autophagy to participate in polycystic ovary syndrome

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110583
Author(s):  
Xiaodong Luo ◽  
Yangyang Gong ◽  
Liuyun Cai ◽  
Lei Zhang ◽  
Xiaojing Dong
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Mammalian Target Of Rapamycin ◽  
Ectopic Expression ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Phosphoinositide 3 Kinase

Objective Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. Chemerin has recently been discovered as a novel adipokine associated with obesity and metabolic syndrome. Excessive autophagy activity and overexpression of autophagy-related genes in follicular granulosa cells are important mechanisms of PCOS. This study aimed to investigate the effect of chemerin on autophagy in PCOS. Methods A rat model of PCOS was established by subcutaneous injection of testosterone propionate under a high-fat diet. Expression levels of chemerin and its receptor CMKLR1 were determined by real-time polymerase chain reaction and western blot. Proliferation and apoptosis of human granulosa cells in vitro and expression of autophagy-related genes were examined using bafilomycin A1 (autophagy inhibitor) and Torin1 (autophagy inducer). Results Chemerin and CMKLR1 expression were significantly increased in the ovary in a rat model of PCOS. Ectopic expression of chemerin promoted the proliferation and inhibited the apoptosis of COV434 cells. Ectopic expression of chemerin also induced autophagy by inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Conclusions Chemerin and CMKLR1 were overexpressed in PCOS rats. Chemerin promoted autophagy through inhibiting the PI3K/Akt/mTOR pathway, and may provide a potential target and biomarker of PCOS.

scholarly journals Effects of Nesfatin-1 and Wnt /β-Catenin Pathway on OGCs in PCOS

2020 ◽  
Author(s):  
Peihui Ding ◽  
Ding-Ding Ai ◽  
Kai-Xue Lao ◽  
Ying Huang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Complex Disease ◽  
Polycystic Ovary ◽  
Hormone Production ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells

Abstract Background Polycystic ovary syndrome is a complex disease related to the endocrine and metabolism. Its specific cause and pathogenesis have not been clear. Nesfatin-1 could not only regulate energy balance and glucose metabolism, but also affect the reproductive system. The Wnt/β-catenin signaling pathway affects follicle development, ovulation, corpus luteum formation, and steroid hormone production. Results Here, we studied the roles of nesfatin-1 and Wnt/β-catenin signaling pathway in the pathogenesis of polycystic ovary syndrome. Firstly, the human primary ovarian granulosa cells in vitro was cultured. The results showed that the apoptosis rate of ovarian granulosa cells in polycystic ovary syndrome patients was significantly higher than that of granular cells in normal people. Moreover, nesfatin-1 and Wnt/β-catenin pathway inhibitor IWR-1could inhibit the expressions of ovarian granulosa cells apoptosis genes and promote their proliferation, as well as nesfatin-1 affected the expressions of foxo3a and its downstream factors. Then, an in vitro culture system for ovarian granulosa cells (OGCs) was established by employing a rat model. The results are the same with those mentioned above. Conclusion This strongly proves that the nesfatin-1 participates in regulating the apoptosis and proliferation of granulosa cells by the Wnt/β-catenin pathway. According to the role of nesfatin-1 and IWR in polycystic ovary syndrome, nesfatin-1 and Wnt/β-catenin pathway can provide a guideline for the diagnosis and treatment of Polycystic ovary syndrome (PCOS).

scholarly journals Comparison of Oocyte and Embryo Quality in Women With Polycystic Ovary Syndrome and the Control Group Candidate for In Vitro Fertilization and Intracytoplasmic Sperm Injection

2020 ◽  
Vol 9 (3) ◽  
pp. 164-170
Author(s):  
Malihe Afiat ◽  
Nayere Khadem ◽  
Elnaz Nayeri ◽  
Roya Jalali ◽  
Saeed Akhlaghi ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Polycystic Ovary Syndrome ◽  
Embryo Quality ◽  
Polycystic Ovary ◽  
Control Group ◽  
Control Groups ◽  
Ovary Syndrome ◽  
Vitro Fertilization ◽  
And Control

Objectives: Polycystic ovary syndrome (PCOS) is the most common cause of female infertility. The aim of this study was to compare the oocyte and embryo quality between the PCOS women with the control group candidate for in vitro fertilization/ intracytoplasmic sperm injection (IVF/ICSI). Materials and Methods: The present study was designed at the Infertility Research Center of Milad in the prospective cohort format and was carried out on 100 cases of infertile women with confirmed PCOS (case group) and the male factor (control group) as the first IVF cycle candidates. Both groups underwent the ovary stimulation cycle and ICSI under the standard antagonist protocol. The collected data were then processed and analyzed using the SPSS software, version 16. Results: The average age of study cases was 35±3, and oocyte necrosis was the underlying pathological factor in both groups (28% and 26% in the PCOS and control groups, respectively). In addition, most embryones belonged to either grade 1 or 2 or were 8-cell embryos. Furthermore, the highest number of transferred embryos among the patients was related to the 8-cell and grade 1. The occurrences of biochemical pregnancy in the PCOS and control groups were up to 31.91% and 22%, respectively, leading to 72.73% and 60% childbirth in cases of both groups. Finally, there were no significant differences observed with respect to the quality and the quantity of the embryones, the oocyte, the transferred embryo, the germinal vesicle oocytes, and the rate of pregnancy among the two groups (P>0.05). Conclusions: According to the results of the present study, no differences were found concerning the oocyte quality, embryo, and the pregnancy rate between PCOS cases and any other patients requiring ICSI. Therefore, such cases can similarly benefit from ICSI methods as well.

scholarly journals The effects of di(2-ethylhexyl) phthalate exposure in women with polycystic ovary syndrome undergoing in vitro fertilization

2019 ◽  
Vol 47 (12) ◽  
pp. 6278-6293 ◽  
Author(s):  
Yue Jin ◽  
Qing Zhang ◽  
Jie-Xue Pan ◽  
Fang-Fang Wang ◽  
Fan Qu
Keyword(s):  
In Vitro Fertilization ◽  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Vitro Fertilization ◽  
Human Granulosa Cells ◽  
Ethylhexyl Phthalate ◽  
Dehp Exposure

Objectives Di(2-ethylhexyl) phthalate (DEHP) is a common endocrine-disrupting chemical, which has potential reproductive toxicity. This study aimed to explore the effects of DEHP exposure in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization. Methods In this case-control study, DEHP levels in follicular fluid (FF) of women with PCOS (n = 56) and controls (n = 51) were measured. The in vitro effects of DEHP exposure on primary-cultured human granulosa cells (GCs) and a steroidogenic human granulosa-like tumor cell line (KGN cells) were analyzed. Results Concentrations of DEHP in FF were significantly higher in women with PCOS than in controls. The clinical pregnancy rate was significantly lower in women with PCOS with high levels of DEHP than in controls. The levels of androgens produced by human GCs were significantly increased following DEHP exposure. Compared with controls, DEHP-treated human GCs and KGN cells showed significantly lower viability, cell cycle arrest, higher apoptosis, and altered expression of apoptosis-related genes. Conclusion Women with PCOS are exposed to increased levels of DEHP in follicles, which may be associated with pregnancy loss following in vitro fertilization. DEHP may disrupt steroid production, balance in cellular proliferation, and apoptosis in human granulosa cells.

scholarly journals ANGPTL4 expression in ovarian granulosa cells is associated with polycystic ovary syndrome

2021 ◽  
Author(s):  
Qi Jiang ◽  
Yanjun Zheng ◽  
Ping Li ◽  
Yuehong Bian ◽  
Wenqi Wang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Clinical Information ◽  
Positive Association ◽  
Control Group ◽  
Ovary Syndrome ◽  
Vitro Fertilization ◽  
Ovarian Granulosa Cells

ABSTRACT Objectives:To characterize the expression of ANGPTL4 in ovarian granulosa cells (GCs) and its association with polycystic ovary syndrome. Design: A retrospective study. Setting: University-based center for reproductive medicine. Participants:This study included 104 PCOS patients and 112 control women undergoing in vitro fertilization-embryo transfer (IVF-ET) from the reproductive hospital affiliated with Shandong University between 2019 and 2021. Methods: The mRNA expression of ANGPTL4 in GCs were assessed by reverse transcription and real-time quantitative (RT-q)PCR, then clinical information for these patients were reviewed and analyzed. Main outcome measures: ANGPTL4 expression in GCs in participants, correlation between ANGPTL4 expression level and metabolic characteristics of patients and predictive value of ANGPTL4 expression for PCOS. Results:The RT-qPCR results showed that ANGPTL4 expression in the control group is significantly lower than that in the PCOS group(P=0.000). It indicated positive association with AMH(r=0.211), HOMA-IR(r=0.174), LDL/HDL(r=0.176), ApoB/ApoAI(r=0.155) and TC/HDL(r=0.189). Additionally, the ANGPTL4 expression in the ovarian granulosa cells might be a independent factor in PCOS(OR:3.345, 95%CI:1.951–5.734) and served as a good predictor for PCOS (AUC0.704, 95%CI 0.633-0.774,P＜0.001). Conclusions:For the first time our study revealed on the higher ANGPTL4 expression in ovarian GCs with PCOS, and its association with glucose and lipid metabolism showed that ANGPTL4 might be a predictor for PCOS and play an important role in metabolism and pathogenesis of PCOS. Funding: National Key R&D Program of China (2018YFC1003202, 2016YFC1000604) and Taishan scholar project special funds (No. ts201712103). Key words: polycystic ovary syndrome, angiopoietin-like protein 4, mRNA, ovarian granulosa cell, glycolipid metabolism

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