scholarly journals Placentas from pregnancies conceived by IVF/ICSI have a reduced DNA methylation level at the H19 and MEST differentially methylated regions†

2013 ◽  
Vol 28 (4) ◽  
pp. 1117-1126 ◽  
Author(s):  
Ewka C.M. Nelissen ◽  
John C.M. Dumoulin ◽  
Antoine Daunay ◽  
Johannes L.H. Evers ◽  
Jörg Tost ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Differentially Methylated Regions

scholarly journals Comparison of Genome-Wide DNA Methylation Profiles of Human Fetal Tissues Conceived by in vitro Fertilization and Natural Conception

2021 ◽  
Vol 9 ◽  
Author(s):  
Ye Liu ◽  
Xinzhu Li ◽  
Songchang Chen ◽  
Li Wang ◽  
Yajing Tan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Metabolic Diseases ◽  
Fetal Tissue ◽  
Thyroid Peroxidase ◽  
Differentially Methylated Regions ◽  
Global Methylation ◽  
Natural Conception ◽  
Ivf Et

BackgroundAssisted reproductive technology (ART) might induce adverse pregnancy outcomes and increase the risk of metabolic diseases in offspring’ later life with unknown reasons. Here we evaluated the global methylation level and methylation profile of fetal tissue from elective terminations of pregnancy (ETP) after natural conception and multifetal pregnancy reduction (MFPR) after in vitro fertilization and embryo transfer (IVF-ET).ResultsGlobal methylation levels were comparable between the fetal tissue of ETP after natural conception group and MFPR after IVF-ET group. The methylation levels were lower in the hypermethylated regions of the MFPR group than in the ETP group, while the methylation levels were higher in the hypomethylated regions of the MFPR group. Heatmap visualization and hierarchical clustering of the candidate differentially methylated regions (DMRs) showed differences between the DMRs in the ETP and MFPR samples. We identified 196 differentially methylated regions that matched 164 genes between the ETP and MFPR groups. In the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, skeletal system morphogenesis and diabetes mellitus ranked first. Ingenuity Pathway Analysis (IPA) revealed 8 diseases and functional annotations associated with IVT-ET. In the MFPR group, the final validation showed lower methylation levels in gene bodies of bone morphogenetic protein 4 (BMP4), higher methylation levels in the 1st exon and 5′UTR of thyroid peroxidase (TPO), and higher methylation levels in TSS1500 and TSS200 of interleukin 1 beta (IL1B).ConclusionsART does not alter global DNA methylation level, but influences DNA methylation variation in specific regions of human fetus in the early stage of life. Further studies are warranted to clarify the potential role of DNA methylation alterations in the gene expression profile.

scholarly journals Profile of copper-associated DNA methylation and its association with incident acute coronary syndrome

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Pinpin Long ◽  
Qiuhong Wang ◽  
Yizhi Zhang ◽  
Xiaoyan Zhu ◽  
Kuai Yu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Acute Coronary Syndrome ◽  
Methylation Level ◽  
Meta Analysis ◽  
Regulation Of Gene Expression ◽  
Density Lipoprotein ◽  
Blood Leukocytes ◽  
Coronary Syndrome ◽  
A Genome ◽  
Increased Risk

Abstract Background Acute coronary syndrome (ACS) is a cardiac emergency with high mortality. Exposure to high copper (Cu) concentration has been linked to ACS. However, whether DNA methylation contributes to the association between Cu and ACS is unclear. Methods We measured methylation level at > 485,000 cytosine-phosphoguanine sites (CpGs) of blood leukocytes using Human Methylation 450 Bead Chip and conducted a genome-wide meta-analysis of plasma Cu in a total of 1243 Chinese individuals. For plasma Cu-related CpGs, we evaluated their associations with the expression of nearby genes as well as major cardiovascular risk factors. Furthermore, we examined their longitudinal associations with incident ACS in the nested case-control study. Results We identified four novel Cu-associated CpGs (cg20995564, cg18608055, cg26470501 and cg05825244) within a 5% false discovery rate (FDR). DNA methylation level of cg18608055, cg26470501, and cg05825244 also showed significant correlations with expressions of SBNO2, BCL3, and EBF4 gene, respectively. Higher DNA methylation level at cg05825244 locus was associated with lower high-density lipoprotein cholesterol level and higher C-reactive protein level. Furthermore, we demonstrated that higher cg05825244 methylation level was associated with increased risk of ACS (odds ratio [OR], 1.23; 95% CI 1.02–1.48; P = 0.03). Conclusions We identified novel DNA methylation alterations associated with plasma Cu in Chinese populations and linked these loci to risk of ACS, providing new insights into the regulation of gene expression by Cu-related DNA methylation and suggesting a role for DNA methylation in the association between copper and ACS.

scholarly journals Associations among phthalate exposure, DNA methylation of TSLP, and childhood allergy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wan-Ru Wang ◽  
Nai-Tzu Chen ◽  
Nai-Yun Hsu ◽  
I-Ying Kuo ◽  
Hsin-Wen Chang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Respiratory Symptoms ◽  
Smoking Status ◽  
Phthalate Esters ◽  
Allergic Diseases ◽  
Percentage Increase ◽  
Phthalate Exposure ◽  
Settled Dust ◽  
Butyl Phthalate

Abstract Background Dysregulation of thymic stromal lymphopoietin (TSLP) expressions is linked to asthma and allergic disease. Exposure to phthalate esters, a widely used plasticizer, is associated with respiratory and allergic morbidity. Dibutyl phthalate (DBP) causes TSLP upregulation in the skin. In addition, phthalate exposure is associated with changes in environmentally induced DNA methylation, which might cause phenotypic heterogeneity. This study examined the DNA methylation of the TSLP gene to determine the potential mechanism between phthalate exposure and allergic diseases. Results Among all evaluated, only benzyl butyl phthalate (BBzP) in the settled dusts were negatively correlated with the methylation levels of TSLP and positively associated with children’s respiratory symptoms. The results revealed that every unit increase in BBzP concentration in the settled dust was associated with a 1.75% decrease in the methylation level on upstream 775 bp from the transcription start site (TSS) of TSLP (β =  − 1.75, p = 0.015) after adjustment for child’s sex, age, BMI, parents’ smoking status, allergic history, and education levels, PM2.5, formaldehyde, temperature; and relative humidity. Moreover, every percentage increase in the methylation level was associated with a 20% decrease in the risk of morning respiratory symptoms in the children (OR 0.80, 95% CI 0.65–0.99). Conclusions Exposure to BBzP in settled dust might increase children’s respiratory symptoms in the morning through decreasing TSLP methylation. Therefore, the exposure to BBzP should be reduced especially for the children already having allergic diseases.

scholarly journals The mediating effect of lifestyles on the association between social factors and DNA methylation

2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
A Maugeri ◽  
M Barchitta ◽  
G Favara ◽  
C La Mastra ◽  
MC La Rosa ◽  
...  
Keyword(s):  
Physical Activity ◽  
Dna Methylation ◽  
Socioeconomic Status ◽  
Mediterranean Diet ◽  
Educational Level ◽  
Methylation Level ◽  
Mediating Effect ◽  
High Educational Level ◽  
Age Related ◽  
High Educational

Abstract Background Social disadvantage and unhealthy lifestyles may induce molecular changes associated with aging and age-related diseases. For instance, previous studies reported socioeconomic difference in DNA methylation, which in turn led to aberrant gene expression and genome instability. Socioeconomic status (SES) alone, however, does not completely explain this difference, and further studies are needed to unveil what factors contribute to it. Methods We conducted a cross-sectional study on 349 Italian women, aged 25-64 years, to assess SES differences in LINE-1 methylation level - a surrogate marker of global DNA methylation - and to examine the mediating effect of lifestyles (i.e. diet, smoking habits, physical activity, and weight status). Educational level was used as SES indicator. The adherence to Mediterranean diet (MD) was assessed by the Mediterranean Diet Score (MDS). Leukocyte LINE-1 methylation was assessed by pyrosequencing. Mediation analysis was conducted using the PROCESS macro for the SPSS software. Results We first observed that women with high educational level were more likely to be normal weight (p < 0.001) and to adhere to MD (p = 0.018), and less likely to perform physical activity (p = 0.012) than their less educated counterpart. Moreover, age-adjusted linear regression demonstrated that LINE-1 methylation level increased with increasing educational level (β = 0.016; SE = 0.003; p < 0.001). In line, mediation analysis demonstrated an indirect effect of high educational level on LINE-1 methylation through the adherence to MD (β = 0.003; 95%CI=0.001-0.006). Specifically, the mediator could account for 9.5% of the total effect. None of the other lifestyles, instead, exhibited a significant mediating effect. Conclusions To our knowledge, this is the first study demonstrating the mediation of diet in the relationship between SES and DNA methylation. Thus, our findings add even more value to the promotion of healthy dietary habits among social disadvantaged people. Key messages Social disadvantage is associated with epigenetic changes related to aging and age-related diseases. Adherence to the Mediterranean diet might mediate the association between socioeconomic status and DNA methylation.

scholarly journals DNA methylation mediated RSPO2 to promote follicular development in mammals

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yingting He ◽  
Nian Li ◽  
Guofeng Bai ◽  
Xiangchun Pan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Wnt Signaling Pathway ◽  
Follicular Development ◽  
Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

PS02.176: LINE-1 METHYLATION LEVEL AND LOCAL IMMUNE RESPONSE IN ESOPHAGEAL CANCER

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 172-172
Author(s):  
Yoshifumi Baba ◽  
Taisuke Yagi ◽  
Yuki Kiyozumi ◽  
Yukiharu Hiyoshi ◽  
Masaaki Iwatsuki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Immune Response ◽  
Esophageal Cancer ◽  
Methylation Level ◽  
Cpg Island ◽  
Surrogate Marker ◽  
Esophageal Tumor ◽  
Local Immune Response ◽  
Dna Hypomethylation ◽  
Response Status

Abstract Background In cancer cells, DNA methylation may be altered in two principle ways; global DNA hypomethylation and site-specific CpG island promoter hypermethylation. Since Long interspersed element-1 (LINE-1 or L1; a repetitive DNA retrotransposon) constitutes a substantial portion (approximately 17%) of the human genome, the extent of LINE-1 methylation is regarded as a surrogate marker of global DNA methylation. In previous studies, we demonstrated that LINE-1 hypomethylation was strongly associated with a poor prognosis in esophageal cancer, supporting its potential role as a prognostic marker (Ann Surg 2012). We also found that LINE-1-hypomethylated tumors showed highly frequent genomic gains at various loci containing candidate oncogenes such as CDK6 (Clin Cancer Res 2014). Given that immunotherapy, as represented by PD-1/PD-L1-targeting antibodies, has increasingly gained attention as a novel treatment strategy for esophageal cancer, better understanding of local immune response status in esophageal cancer is important. The aim of this study is to evaluate the relationship between LINE-1 methylation level and local immune response in esophageal cancer. Methods Using a non-biased database of 305 curatively resected esophageal cancers, we evaluated PD-L1 expression and TIL status (CD8 expression) by immunohistochemical analysis (Ann Surg 2017). Results TIL positivity was significantly correlated with longer overall survival (log-rank P < 0.0001). TIL-negative cases demonstrated significantly lower LINE-1 methylation level compared with TIL-positive cases (P = 0.012). This finding certainly supports that LINE-1 methylation level may influence the local immune response status. Conclusion PD-L1 expression was not related with LINE-1 methylation level. Further investigations in this field would provide deeper insights into esophageal tumor immunology and assist the development of new therapeutic strategies against esophageal cancer. Disclosure All authors have declared no conflicts of interest.

scholarly journals DNA methylation and retinal degenerative diseases: at the crossroad between genes and diet

2020 ◽  
Vol 53 (383) ◽  
pp. MISC1-MISC3
Author(s):  
Andrea Maugeri
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Integrated Approach ◽  
Dietary Factors ◽  
Epigenetic Mechanisms ◽  
Degenerative Diseases ◽  
Retinal Cells ◽  
Significant Difference ◽  
Retinal Degenerative Diseases ◽  
The Impact

Retinal degenerative diseases are the leading causes of blindness and low vision among working-age and older adults worldwide, with 170 and 130 million individuals suffering from age-related macular degeneration (AMD) and diabetic retinopathy, respectively. Although several studies began to show benefits from dietary interventions against retinal degenerative disease, an integrated approach is needed to understand molecular mechanisms underpinning the protective or risky effect of dietary factors. A specific area of research that elucidates mechanisms involved in gene-diet interaction is the Nutri-epigenomics, the study of the impact of diet on gene expression by modulating epigenetic mechanisms. The present research investigated the role of DNA methylation – one of the most commonly analysed epigenetic mechanisms - in the pathophysiology of retinal degenerative diseases, by exploiting a multiple integrated approach. In vitro studies initially helped us to understand how pathological features of retinal degeneration (e.g. oxidative stress, inflammation and hyperglycaemia) modulated functions of enzymes involved in the methylation of Long Interspersed Nuclear Element 1 (LINE-1) sequences in retinal cells. We also proved that some nutrients (e.g. resveratrol and curcumin) might counteract these effects and restore DNA methylation level in retinal cells under oxidative, inflammatory and high glucose conditions. We further analysed whether LINE-1 methylation level differed between patients with AMD and controls without posterior segment eye diseases. Interestingly, we noted a significant difference between the two groups, with higher LINE-1 methylation level in blood samples from AMD patients. This evidence -albeit promising for biomarker discovery- requires confirmation by further large-size prospective studies taking into account different factors. Our research, in fact, also suggested that the risk of retinal degenerative diseases derives from the combination of genetic risk variants, clinical characteristics, environmental exposures and unhealthy lifestyles, which in turn are interrelated. Thus, it would be interesting to study how the exposome -the totality of exposures individuals experience over the course of life- might induce epigenetic mechanisms able to reduce or increase the risk for retinal degenerative diseases.

scholarly journals The Relationship between Body Mass Index, Obesity, and LINE-1 Methylation: A Cross-Sectional Study on Women from Southern Italy

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Giuliana Favara ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Dna Methylation ◽  
Body Mass ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Smoking Status ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
The Relationship

Uncovering the relationship between body mass index (BMI) and DNA methylation could be useful to understand molecular mechanisms underpinning the effects of obesity. Here, we presented a cross-sectional study, aiming to evaluate the association of BMI and obesity with long interspersed nuclear elements (LINE-1) methylation, among 488 women from Catania, Italy. LINE-1 methylation was assessed in leukocyte DNA by pyrosequencing. We found a negative association between BMI and LINE-1 methylation level in both the unadjusted and adjusted linear regression models. Accordingly, obese women exhibited lower LINE-1 methylation level than their normal weight counterpart. This association was confirmed after adjusting for the effect of age, educational level, employment status, marital status, parity, menopause, and smoking status. Our findings were in line with previous evidence and encouraged further research to investigate the potential role of DNA methylation markers in the management of obesity.

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