scholarly journals Multiomics Analysis Reveals Molecular Abnormalities in Granulosa Cells of Women With Polycystic Ovary Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Rusong Zhao ◽  
Yonghui Jiang ◽  
Shigang Zhao ◽  
Han Zhao
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Differentially Expressed ◽  
Steroid Biosynthesis ◽  
Expression Array ◽  
Ovary Syndrome ◽  
Molecular Abnormalities ◽  
Genome Wide

Polycystic ovary syndrome (PCOS) is the most common complex endocrine and metabolic disease in women of reproductive age. It is characterized by anovulatory infertility, hormone disorders, and polycystic ovarian morphology. Regarding the importance of granulosa cells (GCs) in the pathogenesis of PCOS, few studies have investigated the etiology at a single “omics” level, such as with an mRNA expression array or methylation profiling assay, but this can provide only limited insights into the biological mechanisms. Here, genome-wide DNA methylation together with lncRNA-miRNA-mRNA profiles were simultaneously detected in GCs of PCOS cases and controls. A total of 3579 lncRNAs, 49 miRNAs, 669 mRNAs, and 890 differentially methylated regions (DMR)-associated genes were differentially expressed between PCOS cases and controls. Pathway analysis indicated that these differentially expressed genes were commonly associated with steroid biosynthesis and metabolism-related signaling, such as glycolysis/gluconeogenesis. In addition, we constructed ceRNA networks and identified some known ceRNA axes, such as lncRNAs-miR-628-5p-CYP11A1/HSD17B7. We also identified many new ceRNA axes, such as lncRNAs-miR-483-5p-GOT2. Interestingly, most ceRNA axes were also closely related to steroid biosynthesis and metabolic pathways. These findings suggest that it is important to systematically consider the role of reproductive and metabolic genes in the pathogenesis of PCOS.

scholarly journals Understanding Polycystic Ovary Syndrome: A Multifactorial Endocrine Disorder

2021 ◽  
Author(s):  
Surankita Sukul ◽  
Pushkal Sinduvadi Ramesh ◽  
Narahari Agasti
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Genetic Markers ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Reproductive Age ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Ovary Syndrome ◽  
Endocrine Disorder ◽  
Genome Wide

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting a significant population of women of reproductive age group worldwide. Due to the complex pathophysiology and overlapping symptoms, this disorder is often difficult to diagnose. Genome-wide association studies have identified several new risk loci and candidate genes for PCOS. However, currently, there are no standard genetic markers for PCOS susceptibility testing owing to the inconsistent findings. Despite the advent of the genomic era, the challenge to identify and pinpoint the heritable genetic basis of PCOS still exists. This mini-review explores the basic definition and phenotypes of PCOS, the different criteria for the diagnosis, the incidence, gestational complications associated with it, the basis of genetic heritability, and the influence of various gene polymorphisms. Also, this review briefly summarises the reports of genome-wide association studies conducted to identify candidate genetic markers to aid in understanding the complex pathophysiology of PCOS.

scholarly journals Granulosa Cell Survival and Proliferation Are Altered in Polycystic Ovary Syndrome

2008 ◽  
Vol 93 (3) ◽  
pp. 881-887 ◽  
Author(s):  
M. Das ◽  
O. Djahanbakhch ◽  
B. Hacihanefioglu ◽  
E. Saridogan ◽  
M. Ikram ◽  
...  
Keyword(s):  
Gene Expression ◽  
Polycystic Ovary Syndrome ◽  
Cell Survival ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Survival Factor ◽  
Effector Caspase

Abstract Context: Polycystic ovary syndrome (PCOS) represents the most common endocrine abnormality in women of reproductive age. The cause of PCOS remains largely unknown, but studies suggest an intrinsic ovarian abnormality. Objective: The objective of the study was to test our hypothesis that differences in granulosa cell proliferation and apoptosis may underlie abnormalities that affect follicular development. Design: Granulosa cells were prepared from follicular fluid aspirated from 4- to 8-mm follicles of unstimulated ovaries during routine laparoscopy or laparotomy from women with anovulatory PCOS and those with regular ovulatory cycles. Setting: The study was conducted at a university hospital. Patients: Fourteen women with anovulatory PCOS and nine women with regular ovulatory cycles participated in the study. Main Outcome Measures: Immunocytochemistry on granulosa cells to investigate apoptotic and proliferation rates, together with real-time RT-PCR to analyze gene expression profiles of apoptotic regulators, was measured. Results: Significantly lower apoptotic rates were found in granulosa cells from patients with PCOS, compared with women with regular ovulatory cycles (P = 0.004). Lower apoptotic rates were associated with decreased levels of the apoptotic effector caspase-3 (P = 0.001) and increased levels of the anti-apoptotic survival factor cellular inhibitor of apoptosis proteins-2 in the PCOS group that were coupled to higher proliferation rates (P = 0.032). Gene expression profiling confirmed the immunocytochemical findings. Conclusions: Our findings indicate that there are significant differences in the rate of cell death and proliferation in granulosa cell populations in PCOS patients. These are associated with decreased expression of apoptotic effectors and increased expression of a cell survival factor. These results provide new insights that may be useful in developing specific therapeutic intervention strategies in PCOS.

scholarly journals Chemerin regulates autophagy to participate in polycystic ovary syndrome

2021 ◽  
Vol 49 (11) ◽  
pp. 030006052110583
Author(s):  
Xiaodong Luo ◽  
Yangyang Gong ◽  
Liuyun Cai ◽  
Lei Zhang ◽  
Xiaojing Dong
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Mammalian Target Of Rapamycin ◽  
Ectopic Expression ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Phosphoinositide 3 Kinase

Objective Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of reproductive age. Chemerin has recently been discovered as a novel adipokine associated with obesity and metabolic syndrome. Excessive autophagy activity and overexpression of autophagy-related genes in follicular granulosa cells are important mechanisms of PCOS. This study aimed to investigate the effect of chemerin on autophagy in PCOS. Methods A rat model of PCOS was established by subcutaneous injection of testosterone propionate under a high-fat diet. Expression levels of chemerin and its receptor CMKLR1 were determined by real-time polymerase chain reaction and western blot. Proliferation and apoptosis of human granulosa cells in vitro and expression of autophagy-related genes were examined using bafilomycin A1 (autophagy inhibitor) and Torin1 (autophagy inducer). Results Chemerin and CMKLR1 expression were significantly increased in the ovary in a rat model of PCOS. Ectopic expression of chemerin promoted the proliferation and inhibited the apoptosis of COV434 cells. Ectopic expression of chemerin also induced autophagy by inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. Conclusions Chemerin and CMKLR1 were overexpressed in PCOS rats. Chemerin promoted autophagy through inhibiting the PI3K/Akt/mTOR pathway, and may provide a potential target and biomarker of PCOS.

scholarly journals High-Throughput Sequencing Profiles About lncRNAs and mRNAs of Ovarian Granulosa Cells in Polycystic Ovary Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Yanjun Zheng ◽  
Yuehong Bian ◽  
Richao Wu ◽  
Wei Chen ◽  
Linlin Fu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Expression Profiles ◽  
Reproductive Age ◽  
Endocrine Disorders ◽  
Clinical Parameters ◽  
Ovary Syndrome ◽  
Predictive Values ◽  
Ovarian Granulosa Cells

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, which is characterized by ovulatory dysfunction, clinical and/or biochemical androgen excess, polycystic ovaries on ultrasound and genetic heterogeneity. It was well-accepted that many lncRNAs and mRNAs were associated with PCOS, however, remain unclear. Therefore, the purpose of our study was to examine different expression profiles of lncRNAs and mRNAs in ovarian granulosa cells (GCs) in PCOS and Controls, and identify the correlation between lncRNAs, mRNAs and clinical parameters. Sixty five PCOS patients and 65 Controls were enrolled in this study and adopted standard long agonist protocols or GnRH antagonist protocols. Then 6 GCs samples in each group were subjected to high-thoughput sequencing and the remaining samples were used for the further verification by quantitative real-time PCR (qRT-PCR). Gene Oncology (GO), Kyoto Encyclopedia Genes and Genomes (KEGG) enrichment analysis were performed. We predicted the relationship between lncRNAs and mRNAs by Cytoscape software. According to the expression level of lncRNAs, mRNAs and the clinical parameters, we also explored their relationship and evaluate their predictive values for embryos quality and PCOS. We identified 1,049 differential expressed lncRNAs and 3,246 mRNAs (fold-change ≥2, p-value < 0.05). Seven lncRNAs (NONHSAT101926.2, NONHSAT136825.2, NONHSAT227177.1, NONHSAT010538.2, NONHSAT191377.1, NONHSAT230904.1, ENST00000607307) and 3 mRNAs (EREG, ENTPD6, YAP1) were validated consistent with sequence profile. Seven lncRNAs were related to hormone level and follicle counts, 3 mRNAs had connections with lipid metabolism. The area under curve (AUC) of 7 lncRNAs were valuable in distinguishing patients with PCOS from Controls. The AUC of NONHSAT230904.1 and NONHSAT227177.1 were 0.6807 and 0.6410, respectively, for distinguishing whether the rate of high-quality embryos exceeds 50%. Our study showed that the GCs lncRNAs and mRNAs were involved in the occurrence and development of PCOS, which contribute to clarify the pathogenesis mechanism of PCOS.

scholarly journals The Genetic Basis of the Polycystic Ovary Syndrome: A Literature Review Including Discussion ofPPAR-γ

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-23 ◽  
Author(s):  
Ugur Unluturk ◽  
Ayla Harmanci ◽  
Cetin Kocaefe ◽  
Bulent O. Yildiz
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Small Sample Size ◽  
Complex Trait ◽  
Mendelian Inheritance ◽  
Small Sample ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Genome Wide ◽  
Near Future

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS pathogenesis. A large number of functional candidate genes have been tested for association or linkage with PCOS phenotypes with more negative than positive findings. Lack of universally accepted diagnostic criteria, difficulties in the assignment of male phenotype, obscurity in the mode of inheritance, and particularly small sample size of the study populations appear to be major limitations for the genetic studies of PCOS. In the near future, utilizing the genome-wide scan approach and the HapMap project will provide a stronger potential for the genetic analysis of the syndrome.

scholarly journals Role of RAB5A in FSHR-mediated signal transduction in human granulosa cells

Reproduction ◽  
2018 ◽  
Vol 155 (6) ◽  
pp. 505-514 ◽  
Author(s):  
Kai Zhu ◽  
Shang Li ◽  
Jiansheng Liu ◽  
Yan Hong ◽  
Zi-Jiang Chen ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Small Gtpase ◽  
Reproductive Age ◽  
Mrna Levels ◽  
Obese Patients ◽  
Ovary Syndrome ◽  
Human Granulosa Cells ◽  
A Genome

Polycystic ovary syndrome, a common condition characterized by endocrine dysfunction, menstrual irregularity, anovulation and polycystic ovaries, affects 5–7% of reproductive-age women. RAB5B, which is identified by a genome-wide association study as a risk locus for this syndrome, encodes a small GTPase involved in control of receptor internalization and early endosome fusion. We found that RAB5A mRNA levels in luteinized granulosa cells of obese patients with polycystic ovary syndrome were lower than in those of obese women without the syndrome. RAB5A regulated follicle-stimulating hormone (FSH)-mediated translocation of the FSH receptor (FSHR) from the membrane to the cytoplasm and the subsequent FSH–FSHR signaling pathway. We showed that RAB5A negatively regulated aromatase expression and estradiol synthesis in human granulosa cells in association with changes in FSHR levels by way of the cAMP/PKA/CREB pathway. The regulation of FSHR by RAB5A may have been associated with two transcription factors, USF1 and USF2. In conclusion, RAB5A gene was abnormally expressed in luteinized granulosa cells of obese patients with polycystic ovary syndrome, which may help explain high FSHR levels found in this syndrome.

scholarly journals Cangfudaotan Decoction Alleviates Insulin Resistance and Improves Follicular Development in Rats with Polycystic Ovary Syndrome via IGF-1-PI3K/Akt-Bax/Bcl-2 Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Chenye Wang ◽  
Caifei Ding ◽  
Zhoujia Hua ◽  
Chunyue Chen ◽  
Jia Yu
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Cell Apoptosis ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Reproductive Age ◽  
Chemical Components ◽  
Granular Cells ◽  
Ovary Syndrome

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder prevalent in females of reproductive age; insulin resistance (IR) is the major pathogenic driver. Pharmacology is a basic option for PCOS therapy; traditional Chinese medicine (TCM), as a significant part of complementary and alternative medicine, has a long history in the clinical management of PCOS. Cangfudaotan decoction (CFD) has been used clinically for gynaecological diseases especially PCOS. In this study, first, chemical components in CFD were clarified using UPLC-Q/TOF-MS analysis. Then, an animal model of PCOS was established, granular cells were also isolated from the rats with PCOS, and CFD was administrated at different dosages in PCOS rats and granular cells, to investigate the therapeutic effect and mechanisms of CFD for PCOS treatment. The result showed that CFD treatment is effective in PCOS rats and granulosa cells. CFD was able to improve IR, restore the serum hormone levels, inhibit the inflammatory cytokines in PCOS rat, and alleviate ovary morphological injury and apoptosis in PCOS rats. In granulosa cells of PCOS, the result showed that the cell viability was improved, and cell apoptosis was inhibited after CFD administration. Further experiments suggested that CDF improves IR, follicular development, cell apoptosis, and inflammatory microenvironment, and this was associated to the regulation of IGF-1-PI3K/Akt-Bax/Bcl-2 pathway-mediated gene expression. Given that CFD sufficiently suppresses insulin resistance and improves follicular development in this study, exploring these mechanisms might help to optimize the therapeutic treatment of CFD in PCOS patients.

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