Differential Gene Expression Analysis of Oocytes in a PCOS Mouse Model Revealed the Relation of Ribosomal Pathway

Abstract Polycystic ovary syndrome (PCOS), a common endocrinal disorder, is associated with impaired oocyte development, which leads to infertility. However, the pathogenesis of PCOS has not been completely elucidated. This study aimed to analyze the differentially expressed genes (DEGs) and epigenetic changes in the oocytes of the PCOS mouse model to identify the etiological factors. In this study, RNA-sequencing analysis revealed that 90 DEGs were upregulated and 27 DEGs were downregulated in the PCOS mouse model. DNA methylation analysis revealed 30 hypomethylated and 10 hypermethylated regions in the PCOS group. However, the DNA methylation status was not correlated with differential gene expression. The pathway enrichment analysis revealed that five DEGs (Rps21, Rpl36, Rpl36a, Rpl37a, and Rpl22l1) were enriched in ribosome-related pathways in the oocytes of the PCOS mouse model, and the immunohistochemical analysis revealed significantly upregulated expression levels of Rps21 and Rpl36. These results suggest that differential gene expression in the oocytes of the PCOS mouse model is related to impaired folliculogenesis. These findings improved our understanding of the pathogenesis of PCOS.

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Upregulated Ribosomal Pathway Impairs Follicle Development in a Polycystic Ovary Syndrome Mouse Model: Findings of Differential Gene Expression Analysis of Oocytes

10.21203/rs.3.rs-1155132/v1 ◽

2021 ◽

Author(s):

Natsuki Nakanishi ◽

Satoko Osuka ◽

Tomohiro Kono ◽

Hisato Kobayashi ◽

Shinya Ikeda ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Mouse Model ◽

Differential Gene Expression ◽

Polycystic Ovary ◽

Methylation Status ◽

Rna Seq ◽

Ovary Syndrome ◽

Pcos Group ◽

Differential Gene

Abstract Background: Polycystic ovary syndrome (PCOS), a common endocrinal disorder, is associated with impaired oocyte development, which leads to infertility. However, the pathogenesis of PCOS has not been completely elucidated. Limited studies have analyzed the pathological characteristics of oocytes in PCOS. This study aimed to analyze the differentially expressed genes (DEGs) and epigenetic changes in the oocytes of the PCOS mouse model to identify the etiological factors.Methods: C57BL/6J female mice were subcutaneously injected with vehicle or 5α-dihydrotestosterone (250 µg/day) on days 16–18 of pregnancy. Female offspring were used as the control or PCOS group. The oocytes were collected from mice aged 7–9 weeks. The DEGs between the control and PCOS groups were analyzed using RNA sequencing (RNA-Seq). Additionally, the DNA methylation status was analyzed using the post-bisulfite adaptor tagging method. The ovarian tissue sections were stained with hematoxylin and eosin to examine the morphological changes. The proteins, Rps21 and Rpl36, were measured using immunostaining.Results: Compared with the control group, the PCOS group exhibited impaired estrous cycle and polycystic ovary-like morphology. RNA-Seq analysis revealed that 90 DEGs were upregulated and 27 DEGs were downregulated in the PCOS mouse model. DNA methylation analysis revealed 30 hypomethylated and 10 hypermethylated regions in the PCOS group. However, the DNA methylation status was not correlated with differential gene expression. The Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that five DEGs (Rps21, Rpl36, Rpl36a, Rpl37a, and Rpl22l1) were enriched in ribosome-related pathways. The immunohistochemical analysis revealed that the expression levels of Rps21 and Rpl36 were significantly upregulated in the PCOS mouse model.Conclusions: These results suggest that differential gene expression in the oocytes of the PCOS mouse model is related to impaired folliculogenesis. These findings improved our understanding of the pathogenesis of PCOS.

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DNA methylation is not a driver of gene expression reprogramming in young honey bee workers

10.1101/2021.03.12.435154 ◽

2021 ◽

Author(s):

Carlos A. M. Cardoso-Junior ◽

Boris Yagound ◽

Isobel Ronai ◽

Emily J. Remnant ◽

Klaus Hartfelder ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Honey Bee ◽

Differential Gene Expression ◽

Social Contexts ◽

Gene Body ◽

Gene Body Methylation ◽

Differential Gene ◽

Honey Bee Workers ◽

Methylation Patterns

AbstractIntragenic DNA methylation, also called gene body methylation, is an evolutionarily-conserved epigenetic mechanism in animals and plants. In social insects, gene body methylation is thought to contribute to behavioral plasticity, for example between foragers and nurse workers, by modulating gene expression. However, recent studies have suggested that the majority of DNA methylation is sequence-specific, and therefore cannot act as a flexible mediator between environmental cues and gene expression. To address this paradox, we examined whole-genome methylation patterns in the brains and ovaries of young honey bee workers that had been subjected to divergent social contexts: the presence or absence of the queen. Although these social contexts are known to bring about extreme changes in behavioral and reproductive traits through differential gene expression, we found no significant differences between the methylomes of workers from queenright and queenless colonies. In contrast, thousands of regions were differentially methylated between colonies, and these differences were not associated with differential gene expression in a subset of genes examined. Methylation patterns were highly similar between brain and ovary tissues and only differed in nine regions. These results strongly indicate that DNA methylation is not a driver of differential gene expression between tissues or behavioral morphs. Finally, despite the lack of difference in methylation patterns, queen presence affected the expression of all four DNA methyltransferase genes, suggesting that these enzymes have roles beyond DNA methylation. Therefore, the functional role of DNA methylation in social insect genomes remains an open question.

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Integrative analyses of differential gene expression and DNA methylation of ethylbenzene-exposed workers

BioChip Journal ◽

10.1007/s13206-015-9310-4 ◽

2015 ◽

Vol 9 (3) ◽

pp. 259-267 ◽

Cited By ~ 7

Author(s):

Gi Won Kim ◽

Ji Young Hong ◽

So-Yeon Yu ◽

Jeong Jin Ahn ◽

Youngjoo Kim ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Differential Gene Expression ◽

Integrative Analyses ◽

Exposed Workers ◽

Differential Gene

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Postnatal Growth and DNA Methylation Are Associated With Differential Gene Expression of the TACSTD2 Gene and Childhood Fat Mass

Diabetes ◽

10.2337/db11-1039 ◽

2011 ◽

Vol 61 (2) ◽

pp. 391-400 ◽

Cited By ~ 46

Author(s):

A. Groom ◽

C. Potter ◽

D. C. Swan ◽

G. Fatemifar ◽

D. M. Evans ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Differential Gene Expression ◽

Fat Mass ◽

Postnatal Growth ◽

Differential Gene

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Comparative RNA-sequencing profiled the differential gene expression of liver in response to acetyl-CoA carboxylase inhibitor GS-0976 in a mouse model of NASH

PeerJ ◽

10.7717/peerj.8115 ◽

2019 ◽

Vol 7 ◽

pp. e8115

Author(s):

Ying Lu ◽

Xiaolan Su ◽

Manyu Zhao ◽

Qianru Zhang ◽

Chuang Liu ◽

...

Keyword(s):

Gene Expression ◽

Mouse Model ◽

Rna Sequencing ◽

Hepatic Steatosis ◽

Differential Gene Expression ◽

Receptor Interaction ◽

Therapeutic Effects ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Differential Gene

Background Non-alcoholic steatohepatitis (NASH) is a progressive liver disease characterized by hepatic steatosis, lobular inflammation and fibrosis. Acetyl-CoA carboxylase (ACC) isoform 1 and 2 involved in de novo lipogenesis (DNL) and fatty acid oxidation have been identified as a therapeutic target in NASH. GS-0976, the inhibitor of ACC1 and ACC2, has achieved favorable therapeutic effects in clinical trials with NASH. The purpose of this study was to explore the transcriptional alterations regulated by GS-0976 in NASH. Methods C57BL/6 mice were fed on a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) or normal diet for 12 weeks. Mice were treated with or without GS-0976 (3 mg/kg per day) in the last 8 weeks. Oil Red O, Haematoxylin-eosin (H & E), and Sirius Red were used to evaluate hepatic steatosis, inflammation and fibrosis. The comparative RNA-sequencing was conducted to analyse the hepatic gene expression profiles in mice. Reverse transcription–polymerase chain reaction analysis was performed to validate the differential expression of representative genes. Results GS-0976 attenuated the steatosis, inflammation, and fibrosis of NASH in CDAHFD mouse model. High-throughput sequencing and differential gene expression analysis showed that there were 516 up-regulated genes and 525 down-regulated genes after GS-0976 treatment. Genes involved in the metabolic process, extracellular matrix formation, immune response, and angiogenesis were significantly enriched. The “Metabolic pathways” and “ECM-receptor interaction” pathways were the most significantly enriched KEGG pathways in the up-regulated and down-regulated differentially expressed genes (DEGs), respectively. Conclusions Transcriptome analysis showed that GS-0976 could regulate the expression of genes related to metabolism, inflammation and fibrosis in NASH. The global transcriptomic changes in gene expression promote the further understanding for the inhibition mechanisms of GS-0976 in NASH.

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Genetic Profiling of Orbital Fibroblasts from Patients with Graves’ Orbitopathy

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab035 ◽

2021 ◽

Author(s):

Giovanna Rotondo Dottore ◽

Ilaria Bucci ◽

Giulia Lanzolla ◽

Iacopo Dallan ◽

Angela Sframeli ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Cell Proliferation ◽

Differential Gene Expression ◽

Global Dna Methylation ◽

Whole Genome ◽

Graves Orbitopathy ◽

Differential Gene ◽

And Control ◽

Orbital Fibroblasts

Abstract Context Graves’ orbitopathy (GO) is an autoimmune disease that persists when immunosuppression is achieved. Orbital fibroblasts from GO patients display peculiar phenotypes even if not exposed to autoimmunity, possibly reflecting genetic or epigenetic mechanisms, which we investigated here. Objective We aimed to explore potential genetic or epigenetic differences using primary cultures of orbital fibroblasts from GO and control patients. Methods Cell proliferation, hyaluronic acid (HA) secretion, and HA synthases (HAS) were measured. Next-generation sequencing and gene expression analysis of the whole genome were performed, as well as real-time-PCR of selected genes and global DNA methylation assay on orbital fibroblasts from 6 patients with GO and 6 control patients from a referral center. Results Cell proliferation was higher in GO than in control fibroblasts. Likewise, HA in the cell medium was higher in GO fibroblasts. HAS-1 and HAS-2 did not differ between GO and control fibroblasts, whereas HAS-3 was more expressed in GO fibroblasts. No relevant gene variants were detected by whole-genome sequencing. However, 58 genes were found to be differentially expressed in GO compared with control fibroblasts, and RT-PCR confirmed the findings in 10 selected genes. We postulated that the differential gene expression was related to an epigenetic mechanism, reflecting diverse DNA methylation, which we therefore measured. In support of our hypothesis, global DNA methylation was significantly higher in GO fibroblasts. Conclusions We propose that, following an autoimmune insult, DNA methylation elicits differential gene expression and sustains the maintenance of GO.

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