Global DNA methylation loss associated with mercury contamination and aging in the American alligator (Alligator mississippiensis)

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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Global DNA Methylation is influenced by smoking behavior

Pharmacopsychiatry ◽

10.1055/s-2007-991871 ◽

2007 ◽

Vol 40 (05) ◽

Author(s):

MAN Muschler ◽

T Hillemacher ◽

H Frieling ◽

S Moskau ◽

A Semmler ◽

...

Keyword(s):

Dna Methylation ◽

Smoking Behavior ◽

Global Dna Methylation

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

Toxicology Research ◽

10.1093/toxres/tfaa079 ◽

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.

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Evidence of determinate growth in an American alligator ( Alligator mississippiensis ) based on long‐term recapture and osteohistological confirmation

The Anatomical Record ◽

10.1002/ar.24688 ◽

2021 ◽

Author(s):

Thomas R. Rainwater ◽

Holly N. Woodward ◽

Allan R. Woodward ◽

Philip M. Wilkinson

Keyword(s):

Alligator Mississippiensis ◽

American Alligator ◽

Determinate Growth

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Decreased expression of DNA methyltransferases in the testes of patients with non-obstructive azoospermia leads to changes in global DNA methylation levels

Reproduction Fertility and Development ◽

10.1071/rd18246 ◽

2019 ◽

Vol 31 (8) ◽

pp. 1386 ◽

Cited By ~ 1

Author(s):

Fatma Uysal ◽

Gokhan Akkoyunlu ◽

Saffet Ozturk

Keyword(s):

Dna Methylation ◽

Male Infertility ◽

De Novo ◽

Biological Effects ◽

Testicular Biopsy ◽

Round Spermatid ◽

Dna Methyltransferases ◽

Global Dna Methylation ◽

Obstructive Azoospermia ◽

Spermatogenic Cells

DNA methylation plays key roles in epigenetic regulation during mammalian spermatogenesis. DNA methyltransferases (DNMTs) function in de novo and maintenance methylation processes by adding a methyl group to the fifth carbon atom of the cytosine residues within cytosine–phosphate–guanine (CpG) and non-CpG dinucleotide sites. Azoospermia is one of the main causes of male infertility, and is classified as obstructive (OA) or non-obstructive (NOA) azoospermia based on histopathological characteristics. The molecular background of NOA is still largely unknown. DNA methylation performed by DNMTs is implicated in the transcriptional regulation of spermatogenesis-related genes. The aim of the present study was to evaluate the cellular localisation and expression levels of the DNMT1, DNMT3A and DNMT3B proteins, as well as global DNA methylation profiles in testicular biopsy samples obtained from men with various types of NOA, including hypospermatogenesis (hyposperm), round spermatid (RS) arrest, spermatocyte (SC) arrest and Sertoli cell-only (SCO) syndrome. In the testicular biopsy samples, DNMT1 expression and global DNA methylation levels decreased gradually from the hyposperm to SCO groups (P<0.05). DNMT3A expression was significantly decreased in the RS arrest, SC arrest and SCO groups compared with the hyposperm group (P<0.05). DNMT3B expression was significantly lower in the RS arrest and SCO groups than in the hyposperm group (P<0.05). Although both DNMT1 and DNMT3A were localised in the cytoplasm and nucleus of the spermatogenic cells, staining for DNMT3B was more intensive in the nucleus of spermatogenic cells. In conclusion, the findings suggest that significant changes in DNMT expression and global DNA methylation levels in spermatogenic cells may contribute to development of male infertility in the NOA groups. Further studies are needed to determine the molecular biological effects of the altered DNMT expression and DNA methylation levels on development of male infertility.

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Testicular Dnmt3 expression and global DNA methylation are down-regulated by gonadotropin releasing hormones in the ricefield eel Monopterus albus

Scientific Reports ◽

10.1038/srep43158 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 5

Author(s):

Yize Zhang ◽

Xin Sun ◽

Lihong Zhang ◽

Weimin Zhang

Keyword(s):

Dna Methylation ◽

Global Dna Methylation ◽

Monopterus Albus

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

Middle East Fertility Society Journal ◽

10.1186/s43043-021-00066-3 ◽

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.

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