Reproductive technologies for the future: a role for epigenetics

2013 ◽  
Vol 53 (9) ◽  
pp. 954 ◽  
Author(s):  
Caroline G. Walker ◽  
Murray D. Mitchell

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and, subsequently, phenotype, without changing the underlying DNA sequence. It is well established that the environment and nutrition can regulate methylation and, therefore, modify phenotype. In this review, regulation of DNA methylation and in particular, the influence of B-vitamin on one-carbon metabolism is outlined, and how deficiency or supplementation with B-vitamins, such as folate, can influence disease. Evidence is provided for the roles of B-vitamin in regulating reproduction and how deficiency of B-vitamin may be impacting dairy cattle fertility. Results from our laboratory provide evidence for an association between DNA methylation and gene expression in the endometrium during early pregnancy. It is, therefore, hypothesised that DNA methylation may regulate the uterine response to the embryo during early pregnancy and that aberrant DNA methylation during this time may jeopardise pregnancy success. Further research is required to establish if B-vitamin supplementation can improve reproductive success and if this effect is via changes to DNA methylation and gene expression in the endometrium, or via positive effects on oocyte and embryo development.

2005 ◽  
Vol 92 (6) ◽  
pp. 1165-1172 ◽  
Author(s):  
M Murai ◽  
M Toyota ◽  
A Satoh ◽  
H Suzuki ◽  
K Akino ◽  
...  

2018 ◽  
Vol 40 (01) ◽  
pp. 62-70 ◽  
Author(s):  
Alexander Schenk ◽  
Walter Pulverer ◽  
Christine Koliamitra ◽  
Claus Bauer ◽  
Suzana Ilic ◽  
...  

AbstractPositive effects of exercise on cancer prevention and progression have been proposed to be mediated by stimulating natural killer (NK) cells. Because NK cell receptors are regulated by epigenetic modifications, we investigated whether acute aerobic exercise and training change promoter DNA methylation and gene expression of the activating KIR2DS4 and the inhibiting KIR3DL1 gene. Sixteen healthy women (50–60 years) performed a graded exercise test (GXT) and were randomized into either a passive control group or an intervention group performing a four-week endurance exercise intervention. Blood samples (pre-, post-GXT and post-training) were used for isolation of DNA/RNA of NK cells to assess DNA promoter methylation by targeted deep-amplicon sequencing and gene expression by qRT-PCR. Potential changes in NK cell subsets were determined by flow cytometry. Acute and chronic exercise did not provoke significant alterations of NK cell proportions. Promoter methylation decreased and gene expression increased for KIR2DS4 after acute exercise. A high gene expression correlated with a low methylation of CpGs that were altered by acute exercise. Chronic exercise resulted in a minor decrease of DNA methylation and did not alter gene expression. Acute exercise provokes epigenetic modifications, affecting the balance between the activating KIR2DS4 and the inhibiting KIR3DL1, with potential benefits on NK cell function.


2011 ◽  
Vol 165 (2) ◽  
pp. 295-296
Author(s):  
L.F. Starker ◽  
T. Ūerstrup ◽  
G. Westin ◽  
P. Hellman ◽  
R. Udelsman ◽  
...  

Toxics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 338
Author(s):  
Karin Engström ◽  
Yumjirmaa Mandakh ◽  
Lana Garmire ◽  
Zahra Masoumi ◽  
Christina Isaxon ◽  
...  

Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants’ residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.


Author(s):  
Charlotte A.M. Cecil

The biopsychosocial (BPS) model of psychiatry has had a major impact on our modern conceptualization of mental illness as a complex, multi-determined phenomenon. Yet, interdisciplinary BPS work remains the exception, rather than the rule in psychiatry. It has been suggested that this may stem in part from a failure of the BPS model to clearly delineate the mechanisms through which biological, psychological, and social factors co-act in the development of mental illness. This chapter discusses how epigenetic processes that regulate gene expression, such as DNA methylation, are fast emerging as a candidate mechanism for BPS interactions, with potentially widespread implications for the way that psychiatric disorders are understood, assessed, and, perhaps in future, even treated.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2004 ◽  
Author(s):  
Terisha Ghazi ◽  
Thilona Arumugam ◽  
Ashmika Foolchand ◽  
Anil A. Chuturgoon

Cancer initiation and progression is an accumulation of genetic and epigenetic modifications. DNA methylation is a common epigenetic modification that regulates gene expression, and aberrant DNA methylation patterns are considered a hallmark of cancer. The human diet is a source of micronutrients, bioactive molecules, and mycotoxins that have the ability to alter DNA methylation patterns and are thus a contributing factor for both the prevention and onset of cancer. Micronutrients such as betaine, choline, folate, and methionine serve as cofactors or methyl donors for one-carbon metabolism and other DNA methylation reactions. Dietary bioactive compounds such as curcumin, epigallocatechin-3-gallate, genistein, quercetin, resveratrol, and sulforaphane reactivate essential tumor suppressor genes by reversing aberrant DNA methylation patterns, and therefore, they have shown potential against various cancers. In contrast, fungi-contaminated agricultural foods are a source of potent mycotoxins that induce carcinogenesis. In this review, we summarize the existing literature on dietary micronutrients, bioactive compounds, and food-borne mycotoxins that affect DNA methylation patterns and identify their potential in the onset and treatment of cancer.


2015 ◽  
Vol 44 (4) ◽  
pp. 1642-1656 ◽  
Author(s):  
Pierre-Olivier Estève ◽  
Guoqiang Zhang ◽  
V.K. Chaithanya Ponnaluri ◽  
Kanneganti Deepti ◽  
Hang Gyeong Chin ◽  
...  

2017 ◽  
Vol 29 (1) ◽  
pp. 184
Author(s):  
S. Canovas ◽  
E. Ivanova ◽  
S. Garcia-Martinez ◽  
R. Romar ◽  
N. Fonseca-Balvis ◽  
...  

Studies in mouse and human have shown extensive DNA methylation reprogramming in pre-implantation development followed by remethylation from implantation. However, the extent to which such reprogramming is conserved in mammals and the timing of demethylation and remethylation are unknown. As part of a major objective to characterise methylation dynamics in the bovine and porcine species from the oocyte to the blastocyst stage, we aimed here to compare the distribution of methylation at single-base resolution in both species at Day 7.5 of development. The DNA methylation profiles were obtained from individual blastocysts at Day 7.5 [pig: 3 in vivo, 3 in vitro; cow: 3 in vivo, 3 in vitro, 3 inner cell mass (ICM) and 3 trophoectoderm (TE) dissected from in vitro blastocysts] using the post-bisulphite adaptor tagging method and Illumina sequencing. For oocytes, data (GEO: GSE63330) from Schroeder et al. 2015 were analysed. Raw sequences were mapped, methylation calls made using Bismark and data analysis and visualisation was done within the SeqMonk platform. Gene expression profiles from individual blastocysts (3 pig, 3 cow) were obtained by RNA-seq. Annotated mRNA features were quantitated in SeqMonk and these were fed into DESeq2 for differential expression analysis (P < 0.05) as previously reported (Love et al. 2014 Genome Biol. 15, 550). Global methylation levels in whole blastocysts differed substantially between porcine and bovine embryos (in vivo: 12.33 ± 3.6 v. 28.33 ± 3.5%; in vitro: 15.02 ± 3.3 v. 24.41 ± 4.1%). In addition, the distribution of methylation differed: the pattern of cytosine methylated seemed random in the porcine genome, but was highly structured in the bovine genome, with methylation predominantly over gene bodies, resembling the profile previously reported in oocytes (Schroeder et al. 2015 PLoS Genet. 11, e1005442). Regarding correlation analysis, gene expression versus methylation were plotted. It suggested that gene body methylation reflected gene expression pattern in oocytes as well as in bovine blastocysts. Pair-wise comparison of isolated ICM and TE was filtered to require 5% change, and replicate set statistics were applied. This revealed very similar total and regional methylation levels in the 2 compartments, indicating that remethylation does not initiate preferentially in one compartment in bovine pre-implantation embryos. This confirms, from a viewpoint of the genome-wide DNA methylation, what has been observed in mouse for specific genes: the trophoblast-specific DNA methylation occurs after the segregation of the TE and ICM (Nakanishi et al. 2012 Epigenetics 7, 173–183). Our study is the first to provide whole genome methylation profiles from single blastocysts of economically important livestock species. Our data demonstrate that methylation reprogramming in early pre-implantation development is species specific. Knowledge of these specific patterns may have high importance when decisions are taken regarding the use of assisted reproductive technologies, cloning, or generation of transgenic animals. This work was funded by AGL2015–66341-R (MINECO-FEDER), PRX14/00348 (MECD), 19595/EE/14 (F. Séneca).


Epigenomics ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 1845-1859
Author(s):  
Faezeh Maroufi ◽  
Amirhosein Maali ◽  
Meghdad Abdollahpour-Alitappeh ◽  
Mohammad Hossein Ahmadi ◽  
Mehdi Azad

In the last 2 decades, a wide variety of studies have been conducted on epigenetics and its role in various cancers. A major mechanism of epigenetic regulation is DNA methylation, including aberrant DNA methylation variations such as hypermethylation and hypomethylation in the promoters of critical genes, which are commonly detected in tumors and mark the early stages of cancer development. Therefore, epigenetic therapy has been of special importance in the last decade for cancer treatment. In epigenetic therapy, all efforts are made to modulate gene expression to the normal status. Importantly, recent studies have shown that epigenetic therapy is focusing on the new gene editing technology, CRISPR-Cas9. This tool was found to be able to effectively modulate gene expression and alter almost any sequence in the genome of cells, resulting in events such as a change in acetylation, methylation, or histone modifications. Of note, the CRISPR-Cas9 system can be used for the treatment of cancers caused by epigenetic alterations. The CRISPR-Cas9 system has greater advantages than other available methods, including potent activity, easy design and high velocity as well as the ability to target any DNA or RNA site. In this review, we described epigenetic modulators, which can be used in the CRISPR-Cas9 system, as well as their functions in gene expression alterations that lead to cancer initiation and progression. In addition, we surveyed various species of CRISPR-dead Cas9 (dCas9) systems, a mutant version of Cas9 with no endonuclease activity. Such systems are applicable in epigenetic therapy for gene expression modulation through chemical group editing on nucleosomes and chromatin remodeling, which finally return the cell to the normal status and prevent cancer progression.


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