scholarly journals Three-Dimensional Genome Interactions Identify Potential Adipocyte Metabolism-Associated Gene STON1 and Immune-Correlated Gene FSHR at the rs13405728 Locus in Polycystic Ovary Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Can-hui Cao ◽  
Ye Wei ◽  
Rang Liu ◽  
Xin-ran Lin ◽  
Jia-qi Luo ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Expression Patterns ◽  
Three Dimensional ◽  
Ovary Syndrome ◽  
Chromosome Conformation ◽  
3D Genome ◽  
Caucasian Women ◽  
Genome Interactions

Backgroundrs13405728 was identified as one of the most prevalent susceptibility loci for polycystic ovary syndrome (PCOS) in Han Chinese and Caucasian women. However, the target genes and potential mechanisms of the rs13405728 locus remain to be determined.MethodsThree-dimensional (3D) genome interactions from the ovary tissue were characterized via high-through chromosome conformation capture (Hi-C) and Capture Hi-C technologies to identify putative targets at the rs13405728 locus. Combined analyses of eQTL, RNA-Seq, DNase-Seq, ChIP-Seq, and sing-cell sequencing were performed to explore the molecular roles of these target genes in PCOS. PCOS-like mice were applied to verify the expression patterns.ResultsGenerally, STON1 and FSHR were identified as potential targets of the rs13405728 locus in 3D genomic interactions with epigenomic regulatory peaks, with STON1 (P=0.0423) and FSHR (P=0.0013) being highly expressed in PCOS patients. STON1 co-expressed genes were associated with metabolic processes (P=0.0008) in adipocytes (P=0.0001), which was validated in the fat tissue (P<0.0001) and ovary (P=0.0035) from fat-diet mice. The immune system process (GO:0002376) was enriched in FSHR co-expressed genes (P=0.0002) and PCOS patients (P=0.0002), with CD4 high expression in PCOS patients (P=0.0316) and PCOS-like models (P=0.0079). Meanwhile, FSHR expression was positively correlated with CD4 expression in PCOS patients (P=0.0252) and PCOS-like models (P=0.0178). Furthermore, androgen receptor (AR) was identified as the common transcription factor for STON1 and FSHR and positively correlated with the expression of STON1 (P=0.039) and FSHR (P=4e-06) in ovary tissues and PCOS-like mice.ConclusionOverall, we identified STON1 and FSHR as potential targets for the rs13405728 locus and their roles in the processes of adipocyte metabolism and CD4 immune expression in PCOS, which provides 3D genomic insight into the pathogenesis of PCOS.

scholarly journals The DLO Hi-C Tool for Digestion-Ligation-Only Hi-C Chromosome Conformation Capture Data Analysis

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 289 ◽  
Author(s):  
Ping Hong ◽  
Hao Jiang ◽  
Weize Xu ◽  
Da Lin ◽  
Qian Xu ◽  
...  
Keyword(s):  
Target Genes ◽  
High Efficiency ◽  
New Technology ◽  
Three Dimensional ◽  
Large Data ◽  
Regulatory Elements ◽  
Chromosome Conformation Capture ◽  
Genome Chromosome ◽  
Chromosome Conformation ◽  
3D Genome

It is becoming increasingly important to understand the mechanism of regulatory elements on target genes in long-range genomic distance. 3C (chromosome conformation capture) and its derived methods are now widely applied to investigate three-dimensional (3D) genome organizations and gene regulation. Digestion-ligation-only Hi-C (DLO Hi-C) is a new technology with high efficiency and cost-effectiveness for whole-genome chromosome conformation capture. Here, we introduce the DLO Hi-C tool, a flexible and versatile pipeline for processing DLO Hi-C data from raw sequencing reads to normalized contact maps and for providing quality controls for different steps. It includes more efficient iterative mapping and linker filtering. We applied the DLO Hi-C tool to different DLO Hi-C datasets and demonstrated its ability in processing large data with multithreading. The DLO Hi-C tool is suitable for processing DLO Hi-C and in situ DLO Hi-C datasets. It is convenient and efficient for DLO Hi-C data processing.

Increased Expression of KISS1 and KISS1 Receptor in Human Granulosa Lutein Cells—Potential Pathogenesis of Polycystic Ovary Syndrome

2018 ◽  
Vol 26 (11) ◽  
pp. 1429-1438 ◽  
Author(s):  
Kai-Lun Hu ◽  
Hongcui Zhao ◽  
Zheying Min ◽  
Yilei He ◽  
Tianjie Li ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Expression Patterns ◽  
Serum Levels ◽  
Recent Experimental Data ◽  
Ovary Syndrome ◽  
Expression Levels ◽  
Highly Correlated

Kisspeptins are a family of neuropeptides that are essential for fertility. Recent experimental data suggest a putative role of kisspeptin signaling in the direct control of ovarian function. To explore the expression of KISS1 and KISS1 receptor (KISS1R) in human granulosa lutein cells and the potential role of KISS1/KISS1R system in the pathogenesis of polycystic ovary syndrome (PCOS), we measured the concentration of KISS1 in follicular fluid, the expression of KISS1 and KISS1R in granulosa lutein cells, and the circulating hormones. The expression levels of KISS1 and KISS1R were significantly upregulated in human granulosa lutein cells obtained from women with PCOS. The expression levels of KISS1 in human granulosa lutein cells highly correlated with those of KISS1R in non-PCOS patients, but not in patients with PCOS, most likely due to the divergent expression patterns in women with PCOS. Additionally, the expression levels of KISS1 highly correlated with the serum levels of anti-Müllerian hormone (AMH). The expression levels of KISS1 and KISS1R, as well as the follicular fluid levels of KISS1, were not significantly different between the pregnant and nonpregnant patients in both PCOS and non-PCOS groups. In conclusion, the increased expression of KISS1 and KISS1R in human granulosa lutein cells may contribute to the pathogenesis of PCOS. The expression levels of KISS1 highly correlated with the serum levels of AMH. The KISS1 and KISS1R system in the ovary may not have a remarkable role in predicting the in vitro fertilization (IVF) outcome.

Two- and Three-Dimensional Sonographic and Color Doppler Techniques for Diagnosis of Polycystic Ovary Syndrome

2012 ◽  
Vol 31 (7) ◽  
pp. 1015-1024 ◽  
Author(s):  
Cesare Battaglia ◽  
Bruno Battaglia ◽  
Elena Morotti ◽  
Roberto Paradisi ◽  
Isabella Zanetti ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Color Doppler ◽  
Three Dimensional ◽  
Ovary Syndrome ◽  
Doppler Techniques

scholarly journals Role of Exosomal microRNAs and lncRNAs in the Follicular Fluid of Women With Polycystic Ovary Syndrome

2021 ◽  
Author(s):  
Tianmin Ye ◽  
Suxia Lin ◽  
Shufang Ding ◽  
Dandan Cao ◽  
Longdan Luo ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Follicular Fluid ◽  
Target Genes ◽  
Polycystic Ovary ◽  
Signalling Pathway ◽  
Endocrine Disorders ◽  
Ovary Syndrome ◽  
Mapk Signalling Pathway ◽  
Exosomal Mirnas ◽  
Wide Range

Abstract Polycystic ovary syndrome (PCOS) is a complex class of endocrine disorders with insulin resistance, compensatory hyperinsulinaemia and obesity. However, the pathogenesis and therapies of PCOS have not been fully elucidated. Exosomal miRNAs have the potential to serve as biomarkers and therapies for a wide range of medical conditions. In this study, we isolated exosomes from follicular fluid collected from 5 PCOS patients and 5 non-PCOS patients. miRNA cDNA library sequencing identified 124 miRNAs that were significantly upregulated nearly twofold, while 33 miRNAs were significantly downregulated nearly twofold in PCOS follicular fluid exosomes. These miRNA target genes were mainly involved in metabolic pathways, pathways in cancer, the PI3K-Akt signalling pathway, the MAPK signalling pathway, endocytosis, the Ras signalling pathway, the Hippo signalling pathway, and cellular senescence. According to the previously reported exosomal lncRNA data of PCOS follicular fluid, a miRNA and lncRNA coexpression network developed from data from starBase strictly screened 29 differentially expressed miRNAs. This network also helped to identify miRNA signatures associated with metabolic processes in PCOS. Collectively, these results demonstrate the potential pathogenesis of PCOS, and follicular fluid exosomal miRNAs may be efficient targets for the diagnosis and treatment of PCOS in long-term clinical studies.

scholarly journals Endogenous Ovarian Angiogenesis in Polycystic Ovary Syndrome-Like Rats Induced by Low-Frequency Electro-Acupuncture: The CLARITY Three-Dimensional Approach

2018 ◽  
Vol 19 (11) ◽  
pp. 3500 ◽  
Author(s):  
Tong Ma ◽  
Peng Cui ◽  
Xiaoyu Tong ◽  
Wei Hu ◽  
Linus Shao ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Three Dimensional ◽  
Low Frequency ◽  
Corpora Lutea ◽  
Ovary Syndrome ◽  
Follicular Maturation ◽  
Female Wistar Rats ◽  
Follicle Maturation

We sought to determine the role of ovarian vascularity and neo-angiogenesis in the development of mature follicles in polycystic ovary syndrome (PCOS) and to identify any changes induced by low-frequency electro-acupuncture (EA). Twenty-eight 21-day-old female Wistar rats were randomly divided into four groups—Control, Obesity, PCOS-like, and PCOS-like-EA (n = 7/group). Rats in the Obesity group were fed a high-fat diet throughout the experiment. Rats in the PCOS-like and PCOS-like-EA groups were implanted with a sustained-release tube containing 5α-dihydrotestosterone (DHT) beneath the skin of the neck. Rats in the PCOS-like-EA group received low-frequency EA treatment starting at 70 days for 30 min five times a week for four weeks. At the end of the experiment, all rats were euthanized and perfused with hydrogel. The ovaries were collected for clarification and imaging, and ovarian vascularity and neo-angiogenesis were analyzed. Compared with Control and Obesity rats, the ovaries in DHT-induced PCOS-like rats were smaller in size and had fewer mature follicles and corpora lutea. EA increased angiogenesis in the antral follicles of PCOS-like rats, which in turn promoted follicle maturation, ovulation, and CL formation. Therefore, endogenous ovarian angiogenesis plays a very important role in follicular maturation and might be one of the peripheral and direct mechanisms of EA on PCOS.

scholarly journals A Prospective Study of the Prevalence of the Polycystic Ovary Syndrome in Unselected Caucasian Women from Spain1

2000 ◽  
Vol 85 (7) ◽  
pp. 2434-2438 ◽  
Author(s):  
Miryam Asunción ◽  
Rosa M. Calvo ◽  
José L. San Millán ◽  
José Sancho ◽  
Sergio Avila ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Blood Donation ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Endocrine Disorders ◽  
Androgenic Alopecia ◽  
Hydroxylase Deficiency ◽  
Ovary Syndrome ◽  
Caucasian Women ◽  
21 Hydroxylase Deficiency

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.

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