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

Author(s):  
Wei Wang ◽  
Tian Hua ◽  
Xiaodong Li ◽  
Xinxian Zhang ◽  
Wei Hao

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.

2016 ◽  
Vol 4 (5) ◽  
pp. 845-853
Author(s):  
SamirA.M. Zaahkouk ◽  
◽  
El-YamanyI. El-Zawahiri ◽  
AhmedM. Bawdy ◽  
FatmaA. Eid ◽  
...  

2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Ziyu Zhang ◽  
...  

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.


2020 ◽  
Author(s):  
You Li ◽  
Guohui Xiong ◽  
Jun Tan ◽  
Shudi Wang ◽  
Ziyu Zhang ◽  
...  

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.


2021 ◽  
Author(s):  
Yaping Jiang ◽  
Rui Jiang ◽  
Peng Zhang ◽  
qiong Yu ◽  
Hongping Ba ◽  
...  

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.


2002 ◽  
Vol 87 (8) ◽  
pp. 3971-3976 ◽  
Author(s):  
Alejandro Gonzalez ◽  
Eduardo Abril ◽  
Alfredo Roca ◽  
Maria José Aragón ◽  
Maria José Figueroa ◽  
...  

Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation infertility, hyperandrogenemia, and frequently insulin resistance. This study investigated whether polymorphisms in the CAPN10 gene are related with PCOS etiology. The allelic frequencies and genotypes of CAPN10 polymorphisms UCSNP-44, 43, 19, and 63 were determined in 55 well characterized women with polycystic ovaries and 93 unrelated healthy controls using spectrofluorimetric analyses and real-time PCR. Our data indicate that CAPN10 UCSNP-44 allele is associated with PCOS in the Spanish population (P = 0.01). These results support a role of Calpain 10 gene in PCOS susceptibility in humans.


Author(s):  
Gislaine Satyko Kogure ◽  
Victor Barbosa Ribeiro ◽  
Flávia Ganoa de Oliveira Gennaro ◽  
Rui Alberto Ferriani ◽  
Cristiana Libardi Miranda-Furtado ◽  
...  

Abstract Objective The present study aimed to investigate the physical performance of handgrip strength (HGS) in women with polycystic ovary syndrome (PCOS). Methods A case-control study that included 70 women with PCOS and 93 age-matched healthy women aged between 18 and 47 years with body mass index (BMI) between 18 Kg/m2–39.9 Kg/m2. The serum levels of total testosterone, androstenedione, insulin, estradiol, thyroid-stimulating hormone (TSH), prolactin, sex hormone-binding globulin (SHBG), and 17-hydroxyprogesterone (17-OHP) were measured. The free androgen index (FAI) and the homeostatic model assessment of insulin resistance (HOMA-IR) were calculated. The body composition regions of interest (ROIs) were assessed by dual-energy X-ray absorptiometry (DXA), and the handgrip strength (HGS) was evaluated for both the dominant and the non-dominant hands with a manual Sammons Preston (Bolingbrook, IL, US) bulb dynamometer. Results Women with PCOS had high serum levels of total testosterone (p < 0.01), androstenedione (p = 0.03), and insulin (p < 0.01), as well as high FAI (p < 0.01) and HOMA-IR (p = 0.01) scores. Compared with the non-PCOS group, the PCOS group had greater total lean mass in the dominant hand (p < 0.03) and greater HGS in both the dominant and the non-dominant hands (p < 0.01). The HGS was correlated with lean mass (p < 0.01). Conclusion Women with PCOS have greater HGS. This may be associated with age and BMI, and it may be related to lean mass. In addition, the dominance effect on muscle mass may influence the physical performance regarding HGS in women with PCOS.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2494
Author(s):  
Małgorzata Kałużna ◽  
Magdalena Czlapka-Matyasik ◽  
Aleksandra Bykowska-Derda ◽  
Jerzy Moczko ◽  
Marek Ruchala ◽  
...  

Visceral adipose tissue (VAT) accumulation, is a part of a polycystic ovary syndrome (PCOS) phenotype. Dual-energy x-ray absorptiometry (DXA) provides a gold standard measurement of VAT. This study aimed to compare ten different indirect methods of VAT estimation in PCOS women. The study included 154 PCOS and 68 age- and BMI-matched control women. Subjects were divided into age groups: 18–30 y.o. and 30–40 y.o. Analysis included: body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), waist/height 0.5 (WHT.5R), visceral adipose index (VAI), lipid accumulation product (LAP), and fat mass index (FMI). VAT accumulation, android-to-gynoid ratio (A/G), and total body fat (TBF) was measured by DXA. ROC analysis revealed that WHtR, WHT.5R, WC, BMI, and LAP demonstrated the highest predictive value in identifying VAT in the PCOS group. Lower cut-off values of BMI (23.43 kg/m2) and WHtR (0.45) were determined in the younger PCOS group and higher thresholds of WHtR (0.52) in the older PCOS group than commonly used. Measuring either: WHtR, WHT.5R, WC, BMI, or LAP, could help identify a subgroup of PCOS patients at high cardiometabolic risk. The current observations reinforce the importance of using special cut-offs to identify VAT, dependent on age and PCOS presence.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wanqin Feng ◽  
Yan Zhang ◽  
Yuan Pan ◽  
Yi Zhang ◽  
Minjuan Liu ◽  
...  

Abstract Background The etiology between homocysteine and polycystic ovary syndrome (PCOS) is unclear. In humans, the level of homocysteine is mainly affected by two enzymes: methylene tetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR). While the activity of these two enzymes is mainly affected by three missense mutations, namely C677T (MTHFR), A1298C (MTHFR), and A66G (MTRR). This study aims to examine the association between the three missense mutations and PCOS and investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. Methods A case-control study was designed, comprising 150 people with PCOS and 300 controls. Logistic regression analysis was used to assess the association between the three missense mutations and PCOS. Linear regression analysis was used to assess the association between the three missense mutations and the homocysteine level. Mediation analysis was used to investigate whether the three missense mutations exerted their effect on PCOS by affecting the homocysteine level. Results Following adjustments and multiple rounds of testing, MTHFR A1298C was found to be significantly associated with PCOS in a dose-dependent manner (compared to AA, OR = 2.142 for AC & OR = 3.755 for CC; P < 0.001). MTRR A66G was nominally associated with PCOS. Mutations in MTHFR A1298C and MTRR A66G were significantly associated with the homocysteine level. Mediation analysis suggested the effect of MTHFR A1298C on PCOS was mediated by homocysteine. Conclusions MTHFR A1298C and MTRR A66G were associated with PCOS, and MTHFR A1298C might affect the risk of PCOS by influencing the homocysteine level.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Li Yu ◽  
Miao Liu ◽  
Zhenxin Wang ◽  
Te Liu ◽  
Suying Liu ◽  
...  

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.


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