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 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 ◽  
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 Lipidomics analysis of human follicular fluid form normal-weight patients with polycystic ovary syndrome: a pilot study

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yanna Ban ◽  
Haiying Ran ◽  
Ying Chen ◽  
Li Ma
Keyword(s):  
Pilot Study ◽  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Lipid Analysis ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Control Group ◽  
Potential Candidate ◽  
Ovary Syndrome ◽  
Pcos Group

Abstract Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this pilot study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight. Methods Follicular fluid samples were collected from patients who underwent IVF, including normal-weight women without PCOS (control group, n = 10) and normal-weight women with PCOS (PCOS group, n = 8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. Results All 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC < 0.67, p-value < 0.05 and VIP value > 1. These differential species of lipid belong to lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI). Conclusion The identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal-weight.

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 Lipidomics Analysis of Human Follicular Fluid Form Normal-weight Patients With Polycystic Ovary Syndrome

2021 ◽  
Author(s):  
Yanna Ban ◽  
Haiying Ran ◽  
Ying Chen ◽  
Li Ma
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Lipid Analysis ◽  
Polycystic Ovary ◽  
Normal Weight ◽  
Control Group ◽  
P Value ◽  
Potential Candidate ◽  
Ovary Syndrome ◽  
Pcos Group

Abstract Background The polycystic ovary syndrome (PCOS) is the most common endocrine associated with insulin resistance, even in the absence of overweight. The global lipid profile of the follicular fluid in PCOS with normal weight as yet has not been investigated. The objection of this study was to explore the changes of lipids in the follicular fluid of PCOS with normal weight.MethodsFollicular fluid samples were collected from patients who underwent IVF, including normal women (control group, n=10) and normal weight women with PCOS (PCOS group, n=8). A lipidomic analysis was performed by high performance liquid chromatography/ mass spectrometry (HPLC-MS). Multidimensional statistical analysis was performed to disclose the global differences between the two groups. Further, differential lipid analysis between the two groups was performed by Fold Change Analysis (FC Analysis) and T-test to screen potential markers. ResultsAll 812 species of 32 subclasses of lipids were identified by lipidomics analysis. 108 kinds of lipids were considered as the potential candidate differential metabolites with the score of variable importance in the project (VIP) more than 1 by the orthogonal partial least squares discriminant analysis. 32 lipids were significantly different between the PCOS group and the control group simultaneously with FC > 1.5 or FC<0.67, p-value <0.05 and VIP value > 1. These differential metabolites were the lipid subclasses including triglycerides (TG), phosphatidylethanolamines (PE) and phosphatidylinositols (PI).ConclusionThe identified differential lipids in the follicular fluid may be considered as candidate biomarkers as well as therapeutic targets of PCOS with normal weight.

scholarly journals Correlation between steroid levels in follicular fluid and hormone synthesis related substances in its exosomes and embryo quality in patients with polycystic ovary syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Yu ◽  
Miao Liu ◽  
Zhenxin Wang ◽  
Te Liu ◽  
Suying Liu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Mrna Levels ◽  
Hormonal Changes ◽  
Male Factor ◽  
Expression Change ◽  
Ovary Syndrome ◽  
Steroid Synthesis ◽  
Pcos Group

Abstract Background Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder with various manifestations and complex etiology. Follicular fluid (FF) serves as the complex microenvironment for follicular development. However, the correlation between the concentration of steroid in FF and the pathogenesis of PCOS is still unclear. Methods Twenty steroid levels in FF from ten patients with PCOS and ten women with male-factor infertility undergoing in vitro fertilization were tested by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in order to explore their possibly correlation with PCOS. Meanwhile, the mRNA levels of core enzymes in steroid synthesis pathway from exosomes of FF were also detected by qPCR. Results The estriol (p < 0.01), estradiol (p < 0.05) and prenenolone (p < 0.01) levels in FF of PCOS group were significantly increased, compared to the normal group, and the progesterone levels (p < 0.05) were decreased in PCOS group. Increased mRNA levels of CYP11A, CYP19A and HSD17B2 of exosomes were accompanied by the hormonal changes in FF. Correlation analysis showed that mRNA levels of CYP11A and HSD17B2 were negatively correlated with percent of top-quality embryos and rate of embryos develop to blastocyst. Conclusion Our results suggest that increased levels of estrogen and pregnenolone in follicular fluid may affect follicle development in PCOS patients, and the mechanism is partially related to HSD17B1, CYP19A1 and CYP11A1 expression change in FF exosomes.

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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