PAPER OF THE WEEK

Epigenetic prognosis and experiences suffered during childhood

Several scientific papers during 2015 confirmed increasingly clear that the experiences that occurred during our childhood and adolescence remain as epigenetic marks in our body. These marks are also associated with healthy and disease state, such as psychiatric disorders or inflammatory nature. Therefore, the different maternal care you've had, abuse suffered,  or post-traumatic stress you have lived relate to marks on DNA methylation that may be tested to demonstrate post traumatic experiences or use them as forecast for future diseases.

As shown, three recent examples:

1: KM Radtke, Schauer M, HM Gunter Ruf-Leuschner M, J Sill, Meyer A, Elbert T. Epigenetic Modifications of the glucocorticoid receptor gene are Associated With the vulnerability to psychopathology in childhood maltreatment. Psychiatry Transl. 2015 May 26; 5: E571. doi: 10.1038 / tp.2015.63. PubMed PMID: 26,080,088.

2: SR Beach, Lei MK Brody GH, Dogan MV, RA Philibert. Higher levels of protective parenting are Associated With better young adult health: Processes explorationof mediation through epigenetic influences on pro-inflammatory. Front Psychol. 2015 May 28; 6: 676. doi: 10.3389 / fpsyg.2015.00676. eCollection 2015. PubMed PMID: 26.07484 million; PubMed Central PMCID: PMC4446530.

3: Unternaehrer E, AH Meyer, Burkhardt SC, Dempster E, S Staehli, Theill N, Lieb R, Meinlschmidt G. Childhood Associated With maternal care is DNA methylation of the gene for brain-derived neurotrophic factor (BDNF) and oxytocin receptor ( OXTR) in peripheral blood cells in adult men and women. Stress. 2015 June 10: 1-11. [Epub ahead of print] PubMed PMID: 26.0618 million.

Excellent review on epidemiological evidences associated with environmental chemicals and DNA methylation: Progress towards toxicogenomic signatures
Clin Epigenetics. 2015 Apr 29;7(1):55. doi: 10.1186/s13148-015-0055-7. eCollection 2015.

Environmental chemicals and DNA methylation in adults: a systematic review of the epidemiologic evidence.

Author information

  • 1Department of Internal Medicine, Hospital Clínico de Valencia, Avenida Blasco Ibañez, 17, 46010 Valencia, Spain ; Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic de Valencia INCLIVA, Av. Menendez Pelayo 4, Accesorio, 46010 Valencia, Spain.
  • 2Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Department of Internal Medicine, Kidney Institute and Division of Nephrology, China Medical University Hospital and College of Medicine, China Medical University, 2 Yude Road, Taichung, 40447 Taiwan.
  • 3Genotyping and Genetic Diagnosis Unit, Institute for Biomedical Research INCLIVA, Av. Menendez Pelayo, 4 Accesorio, 46010 Valencia, Spain.
  • 4Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA.
  • 5Department of Internal Medicine, Hospital Clínico de Valencia, Avenida Blasco Ibañez, 17, 46010 Valencia, Spain ; Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic de Valencia INCLIVA, Av. Menendez Pelayo 4, Accesorio, 46010 Valencia, Spain ; CIBER Physiopathology of Obesity and Nutrition (CIBEROBN), Institute of Health Carlos III, Minister of Health, Madrid, Spain.
  • 6Nutrition and Genomics Laboratory, Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, 711 Washington St, Boston, MA 02111-1524 USA ; Instituto Madrileño de Estudios Avanzados en Alimentación, Ctra. de Cantoblanco 8, 28049 Madrid, Spain.
  • 7Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA ; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, 2024 E. Monument Street, Baltimore, 21205 MD USA.
  • 8Area of Cardiometabolic and Renal Risk, Institute for Biomedical Research Hospital Clinic de Valencia INCLIVA, Av. Menendez Pelayo 4, Accesorio, 46010 Valencia, Spain ; Department of Environmental Health Sciences, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 USA.

Abstract

Current evidence supports the notion that environmental exposures are associated with DNA-methylation and expression changes that can impact human health. Our objective was to conduct a systematic review of epidemiologic studies evaluating the association between environmental chemicals with DNA methylation levels in adults. After excluding arsenic, recently evaluated in a systematic review, we identified a total of 17 articles (6 on cadmium, 4 on lead, 2 on mercury, 1 on nickel, 1 on antimony, 1 on tungsten, 5 on persistent organic pollutants and perfluorinated compounds, 1 on bisphenol A, and 3 on polycyclic aromatic hydrocarbons). The selected articles reported quantitative methods to determine DNA methylation including immunocolorimetric assays for total content of genomic DNA methylation, and microarray technologies, methylation-specific quantitative PCR, Luminometric Methylation Assay (LUMA), and bisulfite pyrosequencing for DNA methylation content of genomic sites such as gene promoters, LINE-1, Alu elements, and others. Considering consistency, temporality, strength, dose-response relationship, and biological plausibility, we concluded that the current evidence is not sufficient to provide inference because differences across studies and limited samples sizes make it difficult to compare across studies and to evaluate sources of heterogeneity. Important questions for future research include the need for larger and longitudinal studies, the validation of findings, and the systematic evaluation of the dose-response relationships. Future studies should also consider the evaluation of epigenetic marks recently in the research spotlight such as DNA hydroxymethylation and the role of underlying genetic variants.

KEYWORDS:

Bisphenol A; Cadmium; DNA methylation; Environmental chemicals; Lead; Mercury; Metals; Persistent organic pollutants; Polycyclic aromatic hydrocarbons; Systematic review

PMID:
 
25984247
 
[PubMed] 
PMCID:
 
PMC4433069
 
Life-course socioeconomic status leaves an epigenetic signature in cells that it may link to chronic disease risk.
Int J Epidemiol. 2015 Apr 17. pii: dyv060. [Epub ahead of print]

Life-course socioeconomic status and DNA methylation of genes regulating inflammation.

Author information

Abstract

BACKGROUND:

 

In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment.

METHODS:

The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study.

RESULTS:

Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals.

CONCLUSIONS:

Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease risk.

© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

KEYWORDS:

DNA methylation; inflammation; life course; socioeconomic status

PMID:
 
25889032
 
[PubMed - as supplied by publisher]
Maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants.
Int J Epidemiol. 2015 Apr 7. pii: dyv027. [Epub ahead of print]

Exposure to aflatoxin B1 in utero is associated with DNA methylation in white blood cells of infants in The Gambia.

Author information

  • 1Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France, LICAMM, School of Medicine, University of Leeds, Leeds, UK, MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia, Genetic Cancer Susceptibility Group, IARC, Lyon, France, Director, IARC, Lyon, France, MRC Human Nutrition Research, Cambridge, UK and UK Institute of Global Food Security, Queen's University Belfast, Belfast, UK.
  • 2Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France, LICAMM, School of Medicine, University of Leeds, Leeds, UK, MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia, Genetic Cancer Susceptibility Group, IARC, Lyon, France, Director, IARC, Lyon, France, MRC Human Nutrition Research, Cambridge, UK and UK Institute of Global Food Security, Queen's University Belfast, Belfast, UK Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France, LICAMM, School of Medicine, University of Leeds, Leeds, UK, MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia, Genetic Cancer Susceptibility Group, IARC, Lyon, France, Director, IARC, Lyon, France, MRC Human Nutrition Research, Cambridge, UK and UK Institute of Global Food Security, Queen's University Belfast, Belfast, UK.
  • 3Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France, LICAMM, School of Medicine, University of Leeds, Leeds, UK, MRC International Nutrition Group at LSHTM, UK & MRC Keneba, MRC Unit, The Gambia, Genetic Cancer Susceptibility Group, IARC, Lyon, France, Director, IARC, Lyon, France, MRC Human Nutrition Research, Cambridge, UK and UK Institute of Global Food Security, Queen's University Belfast, Belfast, UK medmnr@leeds.ac.uk.

Abstract

BACKGROUND:

Exposure to environmental toxins during embryonic development may lead to epigenetic changes that influence disease risk in later life. Aflatoxin is a contaminant of staple foods in sub-Saharan Africa, is a known human liver carcinogen and has been associated with stunting in infants.

METHODS:

We have measured aflatoxin exposure in 115 pregnant women in The Gambia and examined the DNA methylation status of white blood cells from their infants at 2-8 months old (mean 3.6 ± 0.9). Aflatoxin exposure in women was assessed using an ELISA method to measure aflatoxin albumin (AF-alb) adducts in plasma taken at 1-16 weeks of pregnancy. Genome-wide DNA methylation of infant white blood cells was measured using the Illumina Infinium HumanMethylation450beadchip.

RESULTS:

AF-alb levels ranged from 3.9 to 458.4 pg/mg albumin. We found that aflatoxin exposure in the mothers was associated to DNA methylation in their infants for 71 CpG sites (false discovery rate  0.05), with an average effect size of 1.7% change in methylation. Aflatoxin-associated differential methylation was observed in growth factor genes such as FGF12 and IGF1, and immune-relatedgenes such as CCL28, TLR2 and TGFBI. Moreover, one aflatoxin-associated methylation region (corresponding to the miR-4520b locus) was identified.

CONCLUSIONS:

This study shows that maternal exposure to aflatoxin during the early stages of pregnancy is associated with differential DNA methylation patterns of infants, including in genes related to growth and immune function. This reinforces the need for interventions to reduce aflatoxin exposure, especially during critical periods of fetal and infant development.

© The Author 2015; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

KEYWORDS:

Aflatoxin; DNA methylation; in utero exposure

PMID:
 
25855716
 
[PubMed - as supplied by publisher]
First evidence showing exercise training reprograms the sperm methylome.
Epigenomics. 2015 Apr 13:1-15. [Epub ahead of print]

Genome-wide sperm DNA methylation changes after 3 months of exercise training in humans.

Author information

  • 1Faculty of Science & Technology, Federation University Australia, Y Building, University Drive, Mt Helen, Victoria, Australia 3350.

Abstract

AIM:

DNA methylation programs gene expression and is involved in numerous biological processes. Accumulating evidence supports transgenerational inheritance of DNA methylation changes in mammals via germ cells. Our aim was to determine the effect of exercise on sperm DNA methylation.

MATERIALS & METHODS:

Twenty-four men were recruited and assigned to an exercise intervention or control group. Clinical parameters were measured and sperm samples were donated by subjects before and after the 3-month time-period. Mature sperm global and genome-wide DNA methylation was assessed using an ELISA assay and the 450K BeadChip (Illumina).

RESULTS:

Global and genome-wide sperm DNA methylation was altered after 3 months of exercise training. DNA methylation changes occurred in genes related to numerous diseases such as Schizophrenia and Parkinson's disease.

CONCLUSIONS:

Our study provides the first evidence showing exercise training reprograms the sperm methylome. Whether these DNA methylation changes are inherited to future generations warrants attention.

KEYWORDS:

disease risk; epigenetics; sperm; transgenerational inheritance

PMID:
 
25864559
 
[PubMed - as supplied by publisher]
Some mechanisms involved in Alzheimer's disease may be epigenetically modulated by bioactive food.
J Nutr Health Aging. 2014 Nov;18(9):800-5. doi: 10.1007/s12603-014-0520-6.

Epigenetic nutraceutical diets in Alzheimer's disease.

Author information

  • 1Giovanni Scapagnini, Department of Medicine and Health Sciences, University of Molise, Campobasso 86100, Italy, g.scapagnini@gmail.com.

Abstract

There is growing support that environmental influences and individual genetic susceptibility may increase the incidence and accelerate the onset of Alzheimer's disease (AD). Epigenetic mechanisms encompass a complex regulatory network of modifications with considerable impact on health and disease risk. Abnormal epigenetic regulation is a hallmark in many pathological conditions including AD. It is well recognized that numerous bioactive dietary components mediate epigenetic modifications associated with the pathophysiology of several diseases. Although the influences of dietary factors on epigenetic regulation have been extensively investigated, only few studies have explored the effects of specific food components in regulating epigenetic patterns during neurodegeneration and AD. Epigenetic nutritional research has substantial potential for AD and may represent a window of opportunity to complement other interventions. Here, we provide a brief overview of the main mechanisms involved in AD, some of which may be epigenetically modulated by bioactive food.

PMID:
 
25389957
 
[PubMed - indexed for MEDLINE]
Spanish scientists demonstrate that aberrant sperm DNA methylation might contribute to fertility impairment in couples with unexplained infertility.
Hum Reprod. 2015 Mar 9. pii: dev053. [Epub ahead of print]

Aberrant DNA methylation patterns of spermatozoa in men with unexplained infertility.

Author information

  • 1Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain.
  • 2Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain Department of Immunology and Oncology, National Center for Biotechnology, CNB-CSIC, Cantoblanco, Madrid 28049, Spain.
  • 3Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, Barcelona 08025, Spain.
  • 4Human Molecular Genetics Group-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain affernandez@hca.es slarriba@idibell.cat.
  • 5Cancer Epigenetics Laboratory, Institute of Oncology of Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo 33006, Spain affernandez@hca.es slarriba@idibell.cat.

Abstract

STUDY QUESTION:

Are there DNA methylation alterations in sperm that could explain the reduced biological fertility of male partners from couples with unexplained infertility?

SUMMARY ANSWER:

DNA methylation patterns, not only at specific loci but also at Alu Yb8 repetitive sequences, are altered in infertile individuals compared with fertile controls.

WHAT IS KNOWN ALREADY:

Aberrant DNA methylation of sperm has been associated with human male infertility in patients demonstrating either deficiencies in the process of spermatogenesis or low semen quality.

STUDY DESIGN, SIZE, DURATION:

Case and control prospective study. This study compares 46 sperm samples obtained from 17 normospermic fertile men and 29 normospermic infertile patients.

PARTICIPANTS/MATERIALS, SETTING, METHODS:

Illumina Infinium HD Human Methylation 450K arrays were used to identify genomic regions showing differences in sperm DNA methylation patterns between five fertile and seven infertile individuals. Additionally, global DNA methylation of sperm was measured using the Methylamp Global DNA Methylation Quantification Ultra kit (Epigentek) in 14 samples, and DNA methylation at several repetitive sequences (LINE-1, Alu Yb8, NBL2, D4Z4) measured by bisulfite pyrosequencing in 44 sperm samples. A sperm-specific DNA methylation pattern was obtained by comparing the sperm methylomes with the DNA methylomes of differentiated somatic cells using data obtained from methylation arrays (Illumina 450 K) of blood, neural and glial cells deposited in public databases.

MAIN RESULTS AND THE ROLE OF CHANCE:

In this study we conduct, for the first time, a genome-wide study to identify alterations of spermDNA methylation in individuals with unexplained infertility that may account for the differences in their biological fertility compared with fertile individuals. We have identified 2752 CpGs showing aberrant DNA methylation patterns, and more importantly, these differentially methylated CpGs were significantly associated with CpG sites which are specifically methylated in sperm when compared with somatic cells. We also found statistically significant (P < 0.001) associations between DNA hypomethylation and regions corresponding to those which, in somatic cells, are enriched in the repressive histone mark H3K9me3, and between DNA hypermethylation and regions enriched in H3K4me1 and CTCF, suggesting that the relationship between chromatin context and aberrant DNA methylation of sperm in infertile men could be locus-dependent. Finally, we also show that DNA methylation patterns, not only at specific loci but also at several repetitive sequences (LINE-1, Alu Yb8, NBL2, D4Z4), were lower in sperm than in somatic cells. Interestingly, sperm samples at Alu Yb8 repetitive sequences of infertile patients showed significantly lower DNA methylationlevels than controls.

LIMITATIONS, REASONS FOR CAUTION:

Our results are descriptive and further studies would be needed to elucidate the functional effects of aberrant DNA methylation on male fertility.

WIDER IMPLICATIONS OF THE FINDINGS:

Overall, our data suggest that aberrant sperm DNA methylation might contribute to fertility impairment in couples with unexplained infertility and they provide a promising basis for future research.

STUDY FUNDING/COMPETING INTERESTS:

This work has been financially supported by Fundación Cientifica de la AECC (to R.G.U.); IUOPA (to G.F.B.); FICYT (to E.G.T.); the Spanish National Research Council (CSIC; 200820I172 to M.F.F.); Fundación Ramón Areces (to M.F.F); the Plan Nacional de I+D+I 2008-2011/2013-2016/FEDER (PI11/01728 to AF.F., PI12/01080 to M.F.F. and PI12/00361 to S.L.); the PN de I+D+I 2008-20011 and the Generalitat de Catalunya (2009SGR01490). A.F.F. is sponsored by ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (CP11/00131). S.L. is sponsored by the Researchers Stabilization Program from the Spanish National Health System (CES09/020). The IUOPA is supported by the Obra Social Cajastur, Spain.

© The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

KEYWORDS:

DNA methylation; male infertility; repetitive sequences; sperm; tissue-specific DNA methylation

PMID:
 
25753583
 
[PubMed - as supplied by publisher]
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