scholarly journals Association of air pollution and homocysteine with global DNA methylation: A population-based study from North India

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260860
Author(s):  
Suniti Yadav ◽  
Imnameren Longkumer ◽  
Priyanka Rani Garg ◽  
Shipra Joshi ◽  
Sunanda Rajkumari ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Air Pollution ◽  
Methylation Status ◽  
Population Based ◽  
North India ◽  
Nutritional Deficiencies ◽  
Global Dna Methylation ◽  
Vitamin B ◽  
Global Methylation ◽  
B Vitamin

Background Anthropogenic air pollution has been implicated in aberrant changes of DNA methylation and homocysteine increase (>15μM/L). Folate (<3 ng/mL) and vitamin B12 (<220 pg/mL) deficiencies also reduce global DNA methylation via homocysteine increase. Although B-vitamin supplements can attenuate epigenetic effects of air pollution but such understanding in population-specific studies are lacking. Hence, the present study aims to understand the role of air pollution, homocysteine, and nutritional deficiencies on methylation. Methods We examined cross-sectionally, homocysteine, folate, vitamin B12 (chemiluminescence) and global DNA methylation (colorimetric ELISA Assay) among 274 and 270 individuals from low- and high- polluted areas, respectively, from a single Mendelian population. Global DNA methylation results were obtained on 254 and 258 samples from low- and high- polluted areas, respectively. Results Significant decline in median global DNA methylation was seen as a result of air pollution [high-0.84 (0.37–1.97) vs. low-0.96 (0.45–2.75), p = 0.01]. High homocysteine in combination with air pollution significantly reduced global DNA methylation [high-0.71 (0.34–1.90) vs. low-0.93 (0.45–3.00), p = 0.003]. Folate deficient individuals in high polluted areas [high-0.70 (0.37–1.29) vs. low-1.21 (0.45–3.65)] showed significantly reduced global methylation levels (p = 0.007). In low polluted areas, despite folate deficiency, if normal vitamin B12 levels were maintained, global DNA methylation levels improved significantly [2.03 (0.60–5.24), p = 0.007]. Conversely, in high polluted areas despite vitamin B12 deficiency, if normal folate status was maintained, global DNA methylation status improved significantly [0.91 (0.36–1.63)] compared to vitamin B12 normal individuals [0.54 (0.26–1.13), p = 0.04]. Conclusions High homocysteine may aggravate the effects of air pollution on DNA methylation. Vitamin B12 in low-polluted and folate in high-polluted areas may be strong determinants for changes in DNA methylation levels. The effect of air pollution on methylation levels may be reduced through inclusion of dietary or supplemented B-vitamins. This may serve as public level approach in natural settings to prevent metabolic adversities at community level.

scholarly journals Epigenetic Changes in Equine Embryos After Short-term Storage at Different Temperatures

2021 ◽  
Author(s):  
Gustavo Desire Antunes Gastal ◽  
Dragos Scarlet ◽  
Maria Melchert ◽  
Reinhard Ertl ◽  
Christine Aurich
Keyword(s):  
Dna Methylation ◽  
Growth And Development ◽  
Methylation Status ◽  
Embryo Morphology ◽  
Global Dna Methylation ◽  
Short Term ◽  
Global Methylation ◽  
Short Term Storage ◽  
Maternal Recognition Of Pregnancy ◽  
Term Storage

Abstract Background: In embryos subjected to assisted reproductive techniques, epigenetic modifications may occur that can influence embryonic development and establishment of pregnancy. In horses, the storage temperature during transport of fresh embryos before transfer is a major concern. The aim of this study was to determine the effects of two storage temperatures (5˚C and 20˚C) on equine embryos, collected at day 7 after ovulation and stored for 24 hours, on the following characteristics: (i) morphological and histological development; (ii) expression of candidate genes associated with embryo growth and development, maternal recognition of pregnancy, methylation, and apoptosis; and (iii) gene-specific and global-DNA methylation. Embryos (n=80) were collected from Haflinger mares (n=15) on day 7 (n=60) or day 8 (n=20) after ovulation and assigned to 4 groups: day 7 control (E7F, fresh); day 7, stored for 24h at 5°C (E5C); day 7, stored for 24h at 20°C (E20C); and day 8 control (E8F, fresh 24h time control). The embryos and the storage medium from all groups were analyzed for: (i) medium temperature, pH, and lipid peroxidation (malondialdehyde; MDA), (ii), embryo morphology, mRNA expression, and DNA methylation (immunohistochemistry and gene-specific DNA methylation). Results: Temperature during storage (E5C and E20C) did not affect embryo size (382±47 and 553±99 µm, respectively). There were no changes in pH and MDA accumulation irrespective of group. The relative mRNA abundance of specific genes related to growth and development (POU5F1, SOX2, NANOG), maternal recognition of pregnancy (CYP19A1, PTGES2), DNA methylation (DNMT1, DNMT3A, DNMT3B), and apoptosis (BAX) in the E5C and E20C were either up or downregulated (P<0.05) when compared to controls (E7F and E8F). The global methylation status, even as 5mC and 5hmC immune expression were similar among treatment groups. The specific genes ESR1, NANOG, and DNMT1 were hypomethylated (P<0.001) in E20C embryos when compared to E8F (advanced stage). Conclusions: Therefore, our study demonstrates for the first time the gene-specific and global-DNA methylation status of fresh equine embryos collected on days 7 and 8 after ovulation. In addition, short-term storage, regardless of temperature, modified gene expression and methylation of genes involved in embryo development and may therefore compromise embryo viability and development after transfer.

scholarly journals Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Quan-Fang Chen ◽  
Han Gao ◽  
Qing-Yun Pan ◽  
Ying-Ju Wang ◽  
Xiao-Ning Zhong
Keyword(s):  
Dna Methylation ◽  
Lung Adenocarcinoma ◽  
Single Cell ◽  
Tumor Cells ◽  
Methylation Status ◽  
Cell Junctions ◽  
Global Dna Methylation ◽  
Single Cell Level ◽  
Cell Level ◽  
Global Methylation

AbstractAberrant DNA modifications affect the tumorigenesis and progression of lung cancer. However, the global methylation status of tumor cells and the heterogeneous methylation status of cells within the same tumor need further study. We used publicly available single-cell RNAseq data to investigate the impact and diversity of global methylation status on lung adenocarcinoma. Clustering cells into subgroups and cell differentiation pseudotime analysis, based on expression profile, demonstrated that the global methylation status was crucial to lung adenocarcinoma function and progression. Hypermethylated tumor cells had increased activity related to the hypoxia response. Hyper- and hypomethylated cells indicated upregulation in pathways involving focal adhesion and cell junctions. Pseudotime analysis showed that cell clusters with unique methylation activities were located at the ends of the putative trajectories, suggesting that DNA methylation and demethylation activities were essential to tumor cell progression. Expression of SPP1 was associated with the global methylation status of tumor cells and with patient prognosis. Our study identified the importance and diversity of global DNA methylation status by analysis at the single-cell level. Our findings provide new information about the global DNA methylation status of tumor cells and suggest new approaches for precision medical treatments for lung adenocarcinoma.

scholarly journals Oxidative damage, inflammation, genotoxic effect, and global DNA methylation caused by inhalation of formaldehyde and the purpose of melatonin

2020 ◽  
Vol 9 (6) ◽  
pp. 778-789
Author(s):  
Letícia Bernardini ◽  
Eduardo Barbosa ◽  
Mariele Feiffer Charão ◽  
Gabriela Goethel ◽  
Diana Muller ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Marrow ◽  
Oxidative Damage ◽  
Bronchoalveolar Lavage ◽  
Bone Marrow Cells ◽  
Histological Study ◽  
Global Dna Methylation ◽  
Protective Effects ◽  
Global Methylation ◽  
Protein Thiols

Abstract Formaldehyde (FA) exposure has been proven to increase the risk of asthma and cancer. This study aimed to evaluate for 28 days the FA inhalation effects on oxidative stress, inflammation process, genotoxicity, and global DNA methylation in mice as well as to investigate the potential protective effects of melatonin. For that, analyses were performed on lung, liver and kidney tissues, blood, and bone marrow. Bronchoalveolar lavage was used to measure inflammatory parameters. Lipid peroxidation (TBARS), protein carbonyl (PCO), non-protein thiols (NPSH), catalase activity (CAT), comet assay, micronuclei (MN), and global methylation were determined. The exposure to 5-ppm FA resulted in oxidative damage to the lung, presenting a significant increase in TBARS and NO levels and a decrease in NPSH levels, besides an increase in inflammatory cells recruited for bronchoalveolar lavage. Likewise, in the liver tissue, the exposure to 5-ppm FA increased TBARS and PCO levels and decreased NPSH levels. In addition, FA significantly induced DNA damage, evidenced by the increase of % tail moment and MN frequency. The pretreatment of mice exposed to FA applying melatonin improved inflammatory and oxidative damage in lung and liver tissues and attenuated MN formation in bone marrow cells. The pulmonary histological study reinforced the results observed in biochemical parameters, demonstrating the potential beneficial role of melatonin. Therefore, our results demonstrated that FA exposure with repeated doses might induce oxidative damage, inflammatory, and genotoxic effects, and melatonin minimized the toxic effects caused by FA inhalation in mice.

scholarly journals Potential effect of tobacco cigarettes smoking on global DNA methylation status and protamines transcripts in human spermatozoa

2021 ◽  
Vol 26 (1) ◽  
Author(s):  
Mohammed M. Laqqan ◽  
Maged M. Yassin
Keyword(s):  
Dna Methylation ◽  
Cigarette Smoking ◽  
Dna Fragmentation ◽  
Methylation Status ◽  
Human Spermatozoa ◽  
Global Dna Methylation ◽  
Transcription Level ◽  
Heavy Smokers ◽  
Protamine 1 ◽  
Protamine 2

Abstract Background Epigenetics refers to an alteration in gene expression without alteration in the sequence of DNA and this process may be affected by environmental factors and lifestyle like cigarette smoking. This study was designed to evaluate the potential effect of cigarette smoking on the global DNA methylation status and the transcription level of protamine 1 and protamine 2 in human spermatozoa. A total of 188 semen samples were collected from men with a mean age of 34.9 ± 5.8 years old (98 heavy smokers and 90 non-smokers). The DNA and RNA were isolated from purified spermatozoa, then the status of global DNA methylation and the transcription level of protamine 1 and protamine 2 were evaluated using ELISA and qPCR, respectively. The chromatin non-condensation and DNA fragmentation in human spermatozoa were evaluated using chromomycin A3 staining and TUNEL assay, respectively. Results A significant increase has been found in the status of global DNA methylation in spermatozoa of heavy smokers compared to non-smokers (7.69 ± 0.69 ng/μl vs. 4.90 ± 0.40 ng/μl, P < 0.001). Additionally, a significant reduction has been found in transcription level of protamine 1 (25.49 ± 0.31 vs. 23.94 ± 0.40, P < 0.001) and protamine 2 (28.27 ± 0.39 vs. 23.45 ± 0.30, P < 0.001) in heavy smokers. A downregulation has been found in the transcription level of protamine 1 and protamine 2 with a fold change of 0.497 and 0.047, respectively. A significant increase has been shown in the level of DNA fragmentation and chromatin non-condensation in heavy smokers compared to non-smokers (P < 0.001). On the other hand, a significant positive correlation has been found between sperm chromatin non-condensation, sperm DNA fragmentation, transcription level of protamine 1, transcription level of protamine 2, and global DNA methylation status (r = 0.304, P < 0.001; r = 0.399, P < 0.001; r = 0.216, P = 0.003; r = 0.494, P < 0.001, respectively). Conclusion Tobacco cigarette smoking has a potential influence on the global DNA methylation and the transcription level of protamine genes in human spermatozoa, and consequently, affect negatively on the semen parameters.

scholarly journals Using a medium-throughput comet assay to evaluate the global DNA methylation status of single cells

2014 ◽  
Vol 5 ◽  
Author(s):  
Angélique Lewies ◽  
Etresia Van Dyk ◽  
Johannes F. Wentzel ◽  
Pieter J. Pretorius
Keyword(s):  
Dna Methylation ◽  
Comet Assay ◽  
Single Cells ◽  
Methylation Status ◽  
Global Dna Methylation

scholarly journals Repeats as global DNA methylation marker in bovine preimplantation embryos

2017 ◽  
Vol 62 (No. 2) ◽  
pp. 43-50 ◽  
Author(s):  
W. Li ◽  
A. Van Soom ◽  
L. Peelman
Keyword(s):  
Dna Methylation ◽  
Mutation Rate ◽  
Methylation Level ◽  
Methylation Status ◽  
Repetitive Sequences ◽  
Cell Types ◽  
Blastocyst Stage ◽  
Repeat Sequence ◽  
Preimplantation Embryos ◽  
Global Dna Methylation

DNA methylation undergoes dynamic changes and is a crucial part of the epigenetic regulation during mammalian early development. To determine the DNA methylation levels in bovine embryos, we applied a bisulfite sequencing based method aimed at repetitive sequences including three retrotransposons (L1_BT, BovB, and ERV1-1-I_BT) and Satellite I. A more accurate estimate of the global DNA methylation level compared to previous methods using only one repeat sequence, like Alu, could be made by calculation of the weighted arithmetic mean of multiple repetitive sequences, considering the copy number of each repetitive sequence. Satellite I and L1_BT showed significant methylation reduction at the blastocyst stage, while BovB and ERV1-1-I_BT showed no difference. The mean methylation level of the repetitive sequences during preimplantation development was the lowest at the blastocyst stage. No methylation difference was found between embryos cultured in 5% and 20% O<sub>2</sub>. Because mutations of CpGs negatively influence the calculation accuracy, we checked the mutation rate of the sequenced CpG sites. Satellite I and L1_BT showed a relatively low mutation rate (1.92 and 3.72% respectively) while that of ERV1-1-I_BT and BovB was higher (11.95 and 24% respectively). Therefore we suggest using a combination of repeats with low mutation rate, taking into account the proportion of each sequence, as a relatively quick marker for the global DNA methylation status of preimplantation stages and possibly also for other cell types.

scholarly journals Influence of tissue, age, and environmental quality on DNA methylation in Alligator mississippiensis

Reproduction ◽  
2014 ◽  
Vol 147 (4) ◽  
pp. 503-513 ◽  
Author(s):  
Benjamin B Parrott ◽  
John A Bowden ◽  
Satomi Kohno ◽  
Jessica A Cloy-McCoy ◽  
Matthew D Hale ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Epigenetic Modification ◽  
Alligator Mississippiensis ◽  
Sentinel Species ◽  
Global Dna Methylation ◽  
American Alligator ◽  
Global Methylation ◽  
Contaminant Exposure ◽  
Liquid Chromatography Tandem Mass

Epigenetic modifications are key mediators of the interactions between the environment and an organism's genome. DNA methylation represents the best-studied epigenetic modification to date and is known to play key roles in regulating transcriptional activity and promoting chromosome stability. Our laboratory has previously demonstrated the utility of the American alligator (Alligator mississippiensis) as a sentinel species to investigate the persistent effects of environmental contaminant exposure on reproductive health. Here, we incorporate a liquid chromatography–tandem mass spectrometry method to directly measure the total (global) proportion of 5-methyl-2′-deoxycytidine (5mdC) in ovarian and whole blood DNA from alligators. Global DNA methylation in ovaries was significantly elevated in comparison with that of whole blood. However, DNA methylation appeared similar in juvenile alligators reared under controlled laboratory conditions but originating from three sites with dissimilar environmental qualities, indicating an absence of detectable site-of-origin effects on persistent levels of global 5mdC content. Analyses of tissues across individuals revealed a surprising lack of correlation between global methylation levels in blood and ovary. In addition, global DNA methylation in blood samples from juvenile alligators was elevated compared with those from adults, suggesting that age, as observed in mammals, may negatively influence global DNA methylation levels in alligators. To our knowledge, this is the first study examining global levels of DNA methylation in the American alligator and provides a reference point for future studies examining the interplay of epigenetics and environmental factors in a long-lived sentinel species.

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