scholarly journals Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Ziyu Zhang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Expression Levels ◽  
Pcos Group ◽  
Hh Signaling

Abstract The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOS. Herein, we carried out RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls, and found that Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS group. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group were significantly higher than those in the control group. These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

scholarly journals Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Ziyu Zhang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Control Group ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells ◽  
Pcos Group

Abstract The molecular mechanism that triggers polycystic ovary syndrome is mysterious. Abnormal ovarian granulosa cells are one of the causes of PCOS. Therefore, we carried out RNA-seq in ovarian granulosa cells from patients with PCOS and normal controls and found that Hedgehog signaling pathway members Ihh and ptch2 were abnormally highly expressed in the PCOS group. Granulosa cells from 22 patients with PCOS and 21 controls with normal ovulation were collected. Subsequent qPCR tests also indicated that the expression of ptch1, gli1, and gli2 of other downstream members of Hh in the PCOS group was significantly higher than that in the control group. These results indicate that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

scholarly journals Aberrant Activation of the Hedgehog Signaling Pathway in Granulosa Cells from Patients with Polycystic Ovary Syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Qiongfang Wu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Control Group ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells ◽  
Pcos Group ◽  
Hh Signaling

Abstract The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOS. Herein, we carried out RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls, and found that Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PCOS group. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysis. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group were significantly higher than those in the control group. Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cells. These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

scholarly journals Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Qiongfang Wu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Hedgehog Signaling ◽  
Polycystic Ovary ◽  
Control Group ◽  
Hedgehog Signaling Pathway ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells ◽  
Hh Signaling

Abstract Objective The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOSMethods The study was carried out by using RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysisResults The results found Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PT. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group (PT) were significantly higher than those in the control group (NT). Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cellsConclusions These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.

scholarly journals TNFR1 is Upregulated and Mediates Apoptosis in Cumulus Cells of Women With Polycystic Ovarian Syndrome

2021 ◽  
Author(s):  
Yaping Jiang ◽  
Rui Jiang ◽  
Peng Zhang ◽  
qiong Yu ◽  
Hongping Ba ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Cumulus Cells ◽  
Control Group ◽  
Ovary Syndrome ◽  
Tnf Α ◽  
Pcos Group

Abstract Purpose To investigate the changes of human granulosa cell, TNFR1, TNFR2 and their downstream molecules in patients with polycystic ovary syndrome (PCOS) and the control group. Methods We recruited infertile women with polycystic ovary syndrome (n = 30) and compared them with infertility due to fallopian tube obstruction(n = 30, control group). The ovaries were stimulated with GnRH agonists and gonadotropins. Follicular fluid from large follicles ([14 mm]) was pooled and granulosa cells (GCs) were separated by a cellular filter. The TNF-α level of follicular fluid was measured by ELISA. TUNEL assay were used to detect the apoptosis of purified GCs. Real-time PCR and Western blotting were used to detect the expression of TNF-related signaling molecules in GCs. Results The rate of high quality embryos in the PCOS group was lower than that in the control group. There were higher percentages of apoptosis in GCs of PCOS patients than in the control group. TNF-α is upregulated in follicular fluid of PCOS patients. TNFR1 and caspase-3 mRNA level were signifificantly higher in PCOS group than in the control group. TNF-α-mediated apoptosis of PCOS granulosa cells was mainly dependent on TNFR1.The TNF-α/TNFR1 signaling pathway mediates apoptosis rather than survival in cumulus cells of PCOS patients. Conclusions TNF-α expression was upregulated in follicular fluid of PCOS patients, and TNFR1 overexpression in female granulosa cells of PCOS was associated with higher levels of apoptosis in these cells, suggesting that the TNF-α/TNFR1 signaling pathway may be a candidate for higher apoptosis in female granulosa cells of PCOS.

scholarly journals UCA1 and microRNA-18a signaling pathway mediates the irisin-lowering effect of met in the management of polycystic ovary syndrome (PCOS)

2021 ◽  
Author(s):  
Wei Wang ◽  
Tian Hua ◽  
Xiaodong Li ◽  
Xinxian Zhang ◽  
Wei Hao
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Real Time ◽  
Signaling Pathway ◽  
Real Time Pcr ◽  
Polycystic Ovary ◽  
Luciferase Assay ◽  
Dependent Manner ◽  
Ovary Syndrome ◽  
Lowering Effect ◽  
Pcos Group

IntroductionThe present study aimed to clarify the underlying mechanism of metformin (met) in the management of polycystic ovary syndrome (PCOS) and to explore the role of UCA1/ microRNA-18a signaling pathway in the control of PCOS.Material and methodsReal-time PCR was performed to compare the level of irisin, blood glucose, UCA1 and miR-18a among PCOS, PCOS + Met, and control groups using area under curve (AUC) values. In-silicon analysis and luciferase assay were performed to explore the regulatory relationship among UCA1, miR-18a and irisin. Real-time PCR and Western-blot analysis were carried out to detect the effect of met on the expression of UCA1, miR-18a and irisin.ResultsAUC of UCA1 was the highest while AUC of irisin was the lowest. Also, irisin and UCA1 levels in the PCOS group were much higher than those in the PCOS + Met group, while miR-18a level in the PCOS group was much lower than PCOS + Met group. Through the luciferase assay, miR-18a was proved to directly bound to irisin 3’UTR. Additionally, irisin was identified to be a target gene of miR-18a. Finally, the treatment with met at the increasing concentration reduced the level of UCA1 and irisin but increased the level of miR-18a in a dose dependent manner.ConclusionsIn the management of PCOS, the irisin-lowering effect of met is regulated by the UCA1/miR-18a/RhoB signaling pathway.

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).

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