scholarly journals Silencing Circ_0058063 Enhances Proliferation and Inhibits Apoptosis in PCOS Ovarian Granulosa Cells

2020 ◽  
Author(s):  
Chengcai Wen ◽  
Li Zhang
Keyword(s):  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Endocrine Disease ◽  
Ovarian Granulosa Cells ◽  
Gene And Protein Expression ◽  
Proliferation And Apoptosis ◽  
Pcos Group ◽  
Reproductive Aged Women ◽  
Western Blotting Assay

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women. This study was designed to explore the role of circ_0058063 in PCOS. Methods We recruited 25 PCOS patients and 25 no-PCOS patients. The concentrations of follicle stimulating hormone (FSH), testosterone (T), luteinizing hormone (LH), progesterone (P4) and estradiol (E2) were measured by radioimmunoassay. The level of aromatase was detected using an ELISA kit. The proliferation and apoptosis of ovarian granulosa cells were assessed using CCK-8 assay and flow cytometry, respectively. Gene and protein expression were evaluated through RT-qPCR and Western blotting assay. Results The circ_0058063 level in ovarian granulosa cells and follicular fluid is significantly higher in the PCOS group than the no-PCOS group. Besides, silencing circ_0058063 increases the levels of Aromatase mRNA, P4 and E2 in PCOS ovarian granulosa cells. Additionally, silencing circ_0058063 can promote the proliferation of ovarian granulosa cells in patients with PCOS. Furthermore, silencing circ_0058063 can suppress apoptosis of PCOS ovarian granulosa cells.Conclusions Silencing circ_0058063 enhances proliferation and inhibits apoptosis in PCOS ovarian granulosa cells. Such findings may offer vital insights into a therapeutic target for PCOS.

scholarly journals Silencing circ_0058063 enhances proliferation and inhibits apoptosis in PCOS ovarian granulosa cells

2021 ◽  
Author(s):  
Chengcai Wen ◽  
Li Zhang
Keyword(s):  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Endocrine Disease ◽  
Ovarian Granulosa Cells ◽  
Gene And Protein Expression ◽  
Proliferation And Apoptosis ◽  
Pcos Group ◽  
Reproductive Aged Women ◽  
Western Blotting Assay

Abstract Background Polycystic ovary syndrome (PCOS) is the most common endocrine disease in reproductive-aged women. This study was designed to explore the role of circ_0058063 in PCOS.Methods We recruited nine PCOS patients and nine no-PCOS patients. The concentrations of follicle stimulating hormone (FSH), testosterone (T), luteinizing hormone (LH), progesterone (P4) and estradiol (E2) were measured by radioimmunoassay. The level of aromatase was detected using an ELISA kit. The proliferation and apoptosis of ovarian granulosa cells were assessed using CCK-8 assay and flow cytometry, respectively. Gene and protein expression were evaluated through RT-qPCR and Western blotting assay.Results The circ_0058063 level in ovarian granulosa cells and follicular fluid is significantly higher in the PCOS group than the no-PCOS group. Besides, silencing circ_0058063 increases the levels of Aromatase mRNA, P4 and E2 in PCOS ovarian granulosa cells. Additionally, silencing circ_0058063 can promote the proliferation of ovarian granulosa cells in patients with PCOS. Furthermore, silencing circ_0058063 can suppress apoptosis of PCOS ovarian granulosa cells.Conclusions Silencing circ_0058063 enhances proliferation and inhibits apoptosis in PCOS ovarian granulosa cells. Such findings may offer vital insights into a therapeutic target for PCOS.

scholarly journals Modulation of Cathepsin S (CTSS) Regulates the Secretion of Progesterone and Estradiol, Proliferation, and Apoptosis of Ovarian Granulosa Cells in Rabbits

Animals ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1770
Author(s):  
Guohua Song ◽  
Yixuan Jiang ◽  
Yaling Wang ◽  
Mingkun Song ◽  
Xuanmin Niu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Granulosa Cells ◽  
Hormone Secretion ◽  
Vital Role ◽  
Regulatory Function ◽  
Cathepsin S ◽  
Related Gene ◽  
Ovarian Granulosa Cells ◽  
Proliferation And Apoptosis

Cathepsin S (CTSS) is a member of cysteine protease family. Although many studies have demonstrated the vital role of CTSS in many physiological and pathological processes including tumor growth, angiogenesis and metastasis, the function of CTSS in the development of rabbit granulosa cells (GCS) remains unknown. To address this question, we isolated rabbit GCS and explored the regulatory function of the CTSS gene in cell proliferation and apoptosis. CTSS overexpression significantly promoted the secretion of progesterone (P4) and estrogen (E2) by increasing the expression of STAR and CYP19A1 (p < 0.05). We also found that overexpression of CTSS increased GCS proliferation by up-regulating the expression of proliferation related gene (PCNA) and anti-apoptotic gene (BCL2). Cell apoptosis was markedly decreased by CTSS activation (p < 0.05). In contrast, CTSS knockdown significantly decreased the secretion of P4 and E2 and the proliferation of rabbit GCS, while increasing the apoptosis of rabbit GCS. Taken together, our results highlight the important role of CTSS in regulating hormone secretion, cell proliferation, and apoptosis in rabbit GCS. These results might provide a basis for better understanding the molecular mechanism of rabbit reproduction.

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 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).

Dioscin Ameliorates Polycystic Ovary Syndrome by Inhibiting PI3K/Akt Pathway-Mediated Proliferation and Apoptosis of Ovarian Granulosa Cells

2020 ◽  
Vol 18 (4) ◽  
pp. 331-336
Author(s):  
Xinrong Li ◽  
Beili Lv ◽  
Haiyan Wang ◽  
Qiaohong Qian
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Western Blot ◽  
Granulosa Cells ◽  
Caspase 3 ◽  
Polycystic Ovary ◽  
Akt Pathway ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells ◽  
Proliferation And Apoptosis ◽  
Induced Apoptosis

To understand the mechanism underlying Dioscin inhibition of polycystic ovary syndrome, we have examined its effects on ovarian granulosa cells from letrozole-treated rats. To this end, Western blot was utilized to determine changes in the levels of Bcl-2, cleaved caspase-3, caspase-3, and phosphatidylinositol 3-kinase (PI3K)/protein kinase B pathway after Dioscin treatment in letrozole-treated rats. Dioscin ameliorated polycystic ovary syndrome by reducing the serum level of testosterone and increasing progesterone levels. It also inhibited proliferation and induced apoptosis of ovarian granulosa cells in the rat model by decreasing the level of Bcl-2 and elevating cleaved caspase-3. Western blot analysis revealed that Dioscin suppressed the PI3K/Akt pathway by inhibiting p-AKT/AKT. SC79, a p-AKT/AKT activator, reversed the effects of Dioscin on the proliferation and apoptosis of ovarian granulosa cells. In conclusion, Dioscin might present a novel therapeutic opportunity for patients with polycystic ovary syndrome.

scholarly journals Age-specific cut-off levels of anti-Müllerian hormone can be used as diagnostic markers for polycystic ovary syndrome

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Fahimeh Ramezani Tehrani ◽  
Maryam Rahmati ◽  
Fatemeh Mahboobifard ◽  
Faezeh Firouzi ◽  
Nazanin Hashemi ◽  
...  
Keyword(s):  
Bayesian Method ◽  
Polycystic Ovary ◽  
Characteristic Curve ◽  
Generalized Additive Models ◽  
Additive Models ◽  
Control Group ◽  
Age Group ◽  
Predictive Values ◽  
Pcos Group

Abstract Background The majority of available studies on the AMH thresholds were not age-specific and performed the receiver operating characteristic curve (ROC) analysis, based on variations in sensitivity and specificity rather than positive and negative predictive values (PPV and NPV, respectively), which are more clinically applicable. Moreover, all of these studies used a pre-specified age categorization to report the age-specific cut-off values of AMH. Methods A total of 803 women, including 303 PCOS patients and 500 eumenorrheic non-hirsute control women, were enrolled in the present study. The PCOS group included PCOS women, aged 20–40 years, who were referred to the Reproductive Endocrinology Research Center, Tehran, Iran. The Rotterdam consensus criteria were used for diagnosis of PCOS. The control group was selected among women, aged 20–40 years, who participated in Tehran Lipid and Glucose cohort Study (TLGS). Generalized additive models (GAMs) were used to identify the optimal cut-off points for various age categories. The cut-off levels of AMH in different age categories were estimated, using the Bayesian method. Main results and the role of chance Two optimal cut-off levels of AMH (ng/ml) were identified at the age of 27 and 35 years, based on GAMs. The cut-off levels for the prediction of PCOS in the age categories of 20–27, 27–35, and 35–40 years were 5.7 (95 % CI: 5.48–6.19), 4.55 (95 % CI: 4.52–4.64), and 3.72 (95 % CI: 3.55–3.80), respectively. Based on the Bayesian method, the PPV and NPV of these cut-off levels were as follows: PPV = 0.98 (95 % CI: 0.96–0.99) and NPV = 0.40 (95 % CI: 0.30–0.51) for the age group of 20–27 years; PPV = 0.96 (95 % CI: 0.91–0.99) and NPV = 0.82 (95 % CI: 0.78–0.86) for the age group of 27–35 years; and PPV = 0.86 (95 % CI: 0.80–0.94) and NPV = 0.96 (95 % CI: 0.93–0.98) for the age group of 35–40 years. Conclusions Application of age-specific cut-off levels of AMH, according to the GAMs and Bayesian method, could elegantly assess the value of AMH in discriminating PCOS patients in all age categories.

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