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 ◽  
...  

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.

Author(s):  
Ana Lúcia de Oliveira Bonfá ◽  
Eduardo Donato Alves ◽  
Víctor Fabrício ◽  
Keico Okino Nonaka ◽  
Janete Aparecida Anselmo-Franci ◽  
...  

Polycystic ovary syndrome (PCOS) is one of the most widely recognized endocrine disorders affecting reproductive-age women. The etiopathogenesis and mechanisms of this syndrome remain unclear. Diagnosis requires two of the following: polycystic ovaries, oligo- or anovulation, and hyperandrogenism. Most women with PCOS display conditions such as metabolic abnormalities, diabetes, obesity, cardiovascular disease, and/or bone dysfunction. Considering the ethical limitations of human studies, animal and cell culture models that reflect some features of PCOS are important for investigation of this syndrome. The aim of the present work was to study some of the endocrine relationships between ovaries and bone tissue in a polycystic ovary syndrome animal model. The study was performed using an estradiol valerate PCOS-induced rat model (n = 30) and bone mesenchymal stem cell cultured from bone marrow of those animals. It was hypothesized that changes of the endocrine relationship between ovaries and bones could be observed in from in vivo animal model and in vitro cell culture assays. The ovarian morphological and endocrine changes seem to be correlated with endocrine, biophysical, and biomechanical changes in bone properties. Mesenchymal stem cells obtained from PCOS-induced rats, cultured for up to 21 days and differentiated into osteoblasts, presented lower viability and reduced mineralization of the extracellular matrix. Taken together, these results indicate important endocrine and structural effects of PCOS in ovaries and bones, contributing to part of the understanding of the pathophysiological mechanisms of PCOS.


Author(s):  
Zhongwei Huang ◽  
Eu Leong Yong

Polycystic ovary syndrome (PCOS) is an enigmatic condition and its pathophysiology remains to be determined but it is likely to involve the androgen, insulin, and anti-Mullerian hormone pathways. PCOS is diagnosed in women in the reproductive age group based on the Rotterdam criteria. The spectrum of disease involves various phenotypes based on the current diagnostic criteria and this may have reproductive, metabolic, and endocrine consequences. Reproductive issues include that of irregular menstrual cycles and anovulation. Metabolic disorders such as insulin resistance, obesity, dyslipidaemia, and hypertension must be screened for in all women who are diagnosed with PCOS. Long-term risks of metabolic and endocrine disorders in women with PCOS still need further confirmation with more robust data. Reproductive ageing appears to be increased in women with PCOS and they seem to menopause at a later age. Thus far, PCOS appears to be associated with endometrial hyperplasia and cancer.


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.


2000 ◽  
Vol 85 (7) ◽  
pp. 2434-2438 ◽  
Author(s):  
Miryam Asunción ◽  
Rosa M. Calvo ◽  
José L. San Millán ◽  
José Sancho ◽  
Sergio Avila ◽  
...  

We prospectively estimated the prevalence of the polycystic ovary syndrome (PCOS), as defined by the NIH/NICHHD 1990 endocrine criteria, in a population of 154 Caucasian women of reproductive age reporting spontaneously for blood donation. Anthropometric data; the presence of hirsutism, acne, and androgenic alopecia; and the menstrual history were recorded by a single investigator. In 145 women, blood samples were also obtained for measurement of serum androgen levels. PCOS was defined by the presence of 1) oligomenorrhea, 2) clinical and/or biochemical hyperandrogenism, and 3) exclusion of hyperprolactinemia, thyroid disorders, and nonclassic 21-hydroxylase deficiency. Hirsutism was defined by a modified Ferriman- Gallwey score of 8 or more, acne was considered as a sign of hyperandrogenism when persistent after the second decade of life, and hyperandrogenemia was defined by an increase in circulating testosterone or dehydroepiandrosterone sulfate or an increase in the free androgen index above the 95th percentile of the control values derived from the nonhirsute, nonacneic women having regular menses who were not receiving hormonal therapy. PCOS was present in 10 (6.5%), hirsutism was present in 11 (7.1%), and acne was present in 19 (12.3%) of the 154 women. Our results demonstrate a 6.5% prevalence of PCOS, as defined, in a minimally biased population of Caucasian women from Spain. The polycystic ovary syndrome, hirsutism, and acne are common endocrine disorders in women.


2018 ◽  
Vol 28 (3) ◽  
pp. 151
Author(s):  
Wafa R. AlFatlawi

Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and affect approximately (5-10) % of women of reproductive age. Anti-Müllerian hormone (AMH) is a homodimeric glycoprotein, a member of the transforming growth factor-β superfamily, it is secreted exclusively from women by granulose cells of ovarian follicles and it is considered as the precise marker of follicle pool size. AMH has been shown to be a good surrogate marker for polycystic ovary syndrome (PCOS). Interleukins are considered as strong risk markers of inflammation. Interleukin-36 gamma (IL36) also known as interleukin-1 family member 9 (IL1F9) is a protein that in humans is encoded by the IL36G gene. Serum samples were collected on day 2 of the menstrual cycle. Serum IL36ɣ, FSH and LH concentration were measured by using ELISA. This study aimed to evaluate the association between IL36ɣ and AMH and study the relationship between obesity and AMH of women in the age of reproductive (25-35) yrs. This study included 28 infertile women with PCOS their husbands were apparently normal (hormones and seminal fluid analysis), their aged (25-35) years, and 20 healthy women aged (25-33) years as control. All control women & patients were from outpatients unit of Alkadumia teaching hospital at Baghdad and all the parameters were measured in Sigma Laboratory. Serum IL-36 ɣ elevated in PCOS patients mainly those with high AMH levels. This hormone increased in PCOS patients compared with control. There was a non-significant difference between patients and control to LH and FSH levels.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Beibei Dai ◽  
Jun Jiang

MicroRNA-target networks are often dysregulated in diseases. Our purpose is to investigate this dysregulation of polycystic ovary syndrome (PCOS). Through the bioinformatics reanalysis of the public RNAseq dataset, we found that miR-188-3p was the miRNA with the highest induction rate, and indicated that miR-188-3p might have a rare function of upregulating its targeted expression. This discovery will increase our understanding of the pathology of PCOS and provide new targets for treatment strategies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rusong Zhao ◽  
Yonghui Jiang ◽  
Shigang Zhao ◽  
Han Zhao

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.


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