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 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 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 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 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

scholarly journals Association between Luteinizing Hormone/Choriogonadotropin Receptor Ins18LQ Gene Polymorphism and Polycystic Ovary Syndrome

2020 ◽  
Vol 8 (A) ◽  
pp. 517-520
Author(s):  
Hilma Putri Lubis ◽  
Muhammad Fidel Ganis Siregar ◽  
Ichwanul Adenin ◽  
Binarwan Halim ◽  
Henry Salim Siregar ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Polycystic Ovary Syndrome ◽  
Gene Polymorphism ◽  
Polycystic Ovary ◽  
Control Group ◽  
Control Groups ◽  
Ovary Syndrome ◽  
Significant Difference ◽  
Pcos Group ◽  
And Control

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.

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