scholarly journals The effect of paternal methyl-group donor intake on offspring DNA methylation and birth weight

2017 ◽  
Vol 8 (3) ◽  
pp. 311-321 ◽  
Author(s):  
S. Pauwels ◽  
I. Truijen ◽  
M. Ghosh ◽  
R. C. Duca ◽  
S. A. S. Langie ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Cord Blood ◽  
Gestational Age ◽  
Methylation Status ◽  
Positive Association ◽  
Blood Samples ◽  
Dna Hydroxymethylation ◽  
Methyl Group ◽  
Nutritional Studies

Most nutritional studies on the development of children focus on mother–infant interactions. Maternal nutrition is critically involved in the growth and development of the fetus, but what about the father? The aim is to investigate the effects of paternal methyl-group donor intake (methionine, folate, betaine, choline) on paternal and offspring global DNA (hydroxy)methylation, offspringIGF2DMR DNA methylation, and birth weight. Questionnaires, 7-day estimated dietary records, whole blood samples, and anthropometric measurements from 74 fathers were obtained. A total of 51 cord blood samples were collected and birth weight was obtained. DNA methylation status was measured using liquid chromatography-tandem mass spectrometry (global DNA (hydroxy)methylation) and pyrosequencing (IGF2DMR methylation). Paternal betaine intake was positively associated with paternal global DNA hydroxymethylation (0.028% per 100 mg betaine increase, 95% CI: 0.003, 0.053,P=0.03) and cord blood global DNA methylation (0.679% per 100 mg betaine increase, 95% CI: 0.057, 1.302,P=0.03). Paternal methionine intake was positively associated with CpG1 (0.336% per 100 mg methionine increase, 95% CI: 0.103, 0.569,P=0.006), and mean CpG (0.201% per 100 mg methionine increase, 95% CI: 0.001, 0.402,P=0.049) methylation of theIGF2DMR in cord blood. Further, a negative association between birth weight/birth weight-for-gestational agez-score and paternal betaine/methionine intake was found. In addition, a positive association between choline and birth weight/birth weight-for-gestational agez-score was also observed. Our data indicate a potential impact of paternal methyl-group donor intake on paternal global DNA hydroxymethylation, offspring global andIGF2DMR DNA methylation, and prenatal growth.

scholarly journals Cord Malaria Infection, Complement Activation, Oxidative Stress, Gestational Age, and Birth Weight, Characterized by High Plasmodium falciparum Prevalence in Bamenda, Cameroon

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Oumar Mahamat ◽  
Kidio Gisele Ndum ◽  
Sumo Laurentine ◽  
Ntonifor Ngum Helen
Keyword(s):  
Oxidative Stress ◽  
Birth Weight ◽  
Cord Blood ◽  
Umbilical Cord ◽  
Negative Correlation ◽  
Gestational Age ◽  
Blood Samples ◽  
Total Antioxidant ◽  
Weak Negative Correlation ◽  
And Oxidative Stress

Background. It is unknown whether the presence of Plasmodium falciparum malaria parasites in umbilical cord blood denotes activation of complement and oxidative stress to affect the duration of pregnancy and birth weight. Methods. In a cross-sectional study conducted from January to April 2019 in Bamenda, Cameroon, cord blood samples were collected from 300 women at delivery. Parasitaemia was determined microscopically. Babies’ weight and age of gestation were recorded. Plasma levels of complement and oxidative stress were measured by specific tests. Results. Cord blood malaria prevalence was 21.33%. Babies with an infected cord showed a low birth weight and gestation age than those with uninfected cords. More babies with infected cords had LBW (6.25%) compared to the counterparts (5.50%). The levels of parasitaemia and the babies’ weight showed a weak positive correlation. The prevalence of preterm and postterm birth was 4.33% and 24.33% respectively, with a weak negative correlation between the age of gestation and the umbilical cord parasitaemia. There was correlation between cord parasitaemia and levels of complement haemolytic activity titter (CH50) and specific classical pathway activity (CPA) in cord blood. CH50 and CPA levels, however, were significantly higher in infected cord blood samples, compared with uninfected cord blood samples. CH50 showed a negative correlation with the birth weight and gestational age in infected cord blood samples. The levels of total oxidative stress (TOS) and total antioxidant defense were significantly lower in infected cord blood than uninfected. TOS displayed a positive correlation with the density of parasitaemia and a weak negative correlation with the birth weight and gestational age in infected cord blood. Conclusion. Cord blood infection lowers the complement haemolytic titter, oxygen radicals and total antioxidant defense in neonates. This lowering of complement haemolytic titter and oxygen radical compounds in umbilical cord malaria are associated with low birth weight and preterm birth.

scholarly journals Epigenome-wide contributions to individual differences in childhood phenotypes: A GREML approach

2021 ◽  
Author(s):  
Alexander Neumann ◽  
Jean-Baptiste Pingault ◽  
Janine F. Felix ◽  
Vincent W. V. Jaddoe ◽  
Henning Tiemeier ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Cord Blood ◽  
Gestational Age ◽  
Cross Validation ◽  
Epigenetic Mechanism ◽  
School Age ◽  
Adhd Symptoms ◽  
Cpg Sites ◽  
Variance Explained

Background: DNA methylation is an epigenetic mechanism involved in human development. Numerous epigenome-wide association studies (EWAS) have investigated the associations of DNA methylation at single CpG sites with childhood outcomes. However, the overall contribution of DNA methylation across the genome (R2Methylation) towards childhood phenotypes is unknown. An estimate of R2Methylation would provide context regarding the importance of DNA methylation explaining variance in health outcomes. Methods: We estimated the variance explained by epigenome-wide cord blood methylation (R2Methylation) for five childhood phenotypes: gestational age, birth weight, and body mass index (BMI), IQ and ADHD symptoms at school age. We adapted a genome-based restricted maximum likelihood (GREML) approach with cross-validation (CV) to DNA methylation data and applied it in two population-based birth cohorts: ALSPAC (n=775) and Generation R (n=1382). Results: Using information from >470,000 autosomal probes we estimated that DNA methylation at birth explains 45% (SDCV = 0.07) of gestational age variance and 16% (SDCV = 0.05) of birth weight variance. The R2Methylation estimates for BMI, IQ and ADHD symptoms at school age estimates were near 0% across almost all cross-validation iterations. Conclusions: The results suggest that cord blood methylation explains a moderate to large degree of variance in gestational age and birth weight, in line with the success of previous EWAS in identifying numerous CpG sites associated with these phenotypes. In contrast, we could not obtain a reliable estimate for school-age BMI, IQ and ADHD symptoms. This may reflect a null bias due to insufficient sample size to detect variance explained in more weakly associated phenotypes, although the true R2Methylation for these phenotypes is likely below that of gestational age and birth weight when using DNA methylation at birth.

scholarly journals Prenatal Bisphenol a Exposure, DNA Methylation, and Low Birth Weight: A Pilot Study in Taiwan

2021 ◽  
Vol 18 (11) ◽  
pp. 6144
Author(s):  
Yu-Fang Huang ◽  
Chia-Huang Chang ◽  
Pei-Jung Chen ◽  
I-Hsuan Lin ◽  
Yen-An Tsai ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Bisphenol A ◽  
Cord Blood ◽  
Developmental Disorders ◽  
Metabolic Diseases ◽  
System Development ◽  
Maternal Blood ◽  
Blood Samples

Prenatal exposure to bisphenol A (BPA) may increase the risk of abnormal birth outcomes, and DNA methylation might mediate these adverse effects. This study aimed to investigate the effects of maternal BPA exposure on maternal and fetal DNA methylation levels and explore whether epigenetic changes are related to the associations between BPA and low birth weight. We collected urine and blood samples originating from 162 mother-infant pairs in a Taiwanese cohort study. We measured DNA methylation using the Illumina Infinium HumanMethylation 450 BeadChip in 34 maternal blood samples with high and low BPA levels based on the 75th percentile level (9.5 μg/g creatinine). Eighty-seven CpGs with the most differentially methylated probes possibly interacting with BPA exposure or birth weight were selected using two multiple regression models. Ingenuity pathway analysis (IPA) was utilized to narrow down 18 candidate CpGs related to disease categories, including developmental disorders, skeletal and muscular disorders, skeletal and muscular system development, metabolic diseases, and lipid metabolism. We then validated these genes by pyrosequencing, and 8 CpGs met the primer design score requirements in 82 cord blood samples. The associations among low birth weight, BPA exposure, and DNA methylation were analyzed. Exposure to BPA was associated with low birth weight. Analysis of the epigenome-wide findings did not show significant associations between BPA and DNA methylation in cord blood of the 8 CpGs. However, the adjusted odds ratio for the dehydrogenase/reductase member 9 (DHRS9) gene, at the 2nd CG site, in the hypermethylated group was significantly associated with low birth weight. These results support a role of BPA, and possibly DHRS9 methylation, in fetal growth. However, additional studies with larger sample sizes are warranted.

scholarly journals Putative Epimutagens in Maternal Peripheral and Cord Blood Samples Identified Using Human Induced Pluripotent Stem Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Yoshikazu Arai ◽  
Koji Hayakawa ◽  
Daisuke Arai ◽  
Rie Ito ◽  
Yusuke Iwasaki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Stem Cells ◽  
Cord Blood ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Methylation Status ◽  
Combined Exposure ◽  
Blood Samples ◽  
Low Concentrations ◽  
Induced Pluripotent

The regulation of transcription and genome stability by epigenetic systems are crucial for the proper development of mammalian embryos. Chemicals that disturb epigenetic systems are termed epimutagens. We previously performed chemical screening that focused on heterochromatin formation and DNA methylation status in mouse embryonic stem cells and identified five epimutagens: diethyl phosphate (DEP), mercury (Hg), cotinine, selenium (Se), and octachlorodipropyl ether (S-421). Here, we used human induced pluripotent stem cells (hiPSCs) to confirm the effects of 20 chemicals, including the five epimutagens, detected at low concentrations in maternal peripheral and cord blood samples. Of note, these individual chemicals did not exhibit epimutagenic activity in hiPSCs. However, because the fetal environment contains various chemicals, we evaluated the effects of combined exposure to chemicals (DEP, Hg, cotinine, Se, and S-421) on hiPSCs. The combined exposure caused a decrease in the number of heterochromatin signals and aberrant DNA methylation status at multiple gene loci in hiPSCs. The combined exposure also affected embryoid body formation and neural differentiation from hiPSCs. Therefore, DEP, Hg, cotinine, Se, and S-421 were defined as an “epimutagen combination” that is effective at low concentrations as detected in maternal peripheral and cord blood.

scholarly journals Maternal and Cord Blood Folate Concentrations Are Inversely Associated with Fetal DNA Hydroxymethylation, but Not DNA Methylation, in a Cohort of Pregnant Canadian Women

2019 ◽  
Author(s):  
Lesley Plumptre ◽  
Stephanie A Tammen ◽  
Kyoung-Jin Sohn ◽  
Shannon P Masih ◽  
Carly E Visentin ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Cord Blood ◽  
Early Pregnancy ◽  
Serum Vitamin ◽  
Vitamin B ◽  
Blood Concentrations ◽  
Dna Hydroxymethylation ◽  
Fetal Dna ◽  
Vitamin B 12

ABSTRACT Background Aberrancies in fetal DNA methylation programming may modify disease susceptibility of the offspring. Maternal folate status has potential to alter fetal DNA methylation. Objectives We examined the association of maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA), vitamin B-12, vitamin B-6, and choline with fetal DNA methylation and hydroxymethylation and assessed potential modifying effects of 38 fetal genetic variants in 22 genes. Methods Nutrient blood concentrations were measured in 368 pregnant women in early pregnancy (12–16 wk of gestation) and at delivery (37–42 wk of gestation) and in cord blood. DNA methylation and hydroxymethylation in cord blood mononuclear cells were quantified by LC-MS/MS. Pearson partial correlations were used to determine the association between individual nutrients and DNA methylation and hydroxymethylation. Results Serum and RBC folate and plasma UMFA concentrations (primary outcomes) in early pregnancy, at delivery, and in cord blood were not significantly associated with fetal DNA methylation. In contrast, maternal RBC folate in early pregnancy (r = −0.16, P = 0.04) and cord plasma UMFA (r = −0.23, P = 0.004) were inversely correlated with fetal DNA hydroxymethylation. Neither maternal and cord blood concentrations of other nutrients nor fetal genotypes (secondary outcomes) were significantly associated with fetal DNA methylation or hydroxymethylation. Infants born to mothers with RBC folate concentrations in the highest quartile and serum vitamin B-12 concentrations in the lowest quartile in early pregnancy had significantly lower fetal DNA methylation and higher birth weight compared with those born to mothers with lower RBC folate and higher serum vitamin B-12 concentrations (P = 0.01). Conclusions Maternal and cord blood folate concentrations are associated with fetal DNA hydroxymethylation, but not DNA methylation, in a cohort of pregnant Canadian women. The observation that high folate and low vitamin B-12 maternal status in early pregnancy may be associated with decreased fetal DNA methylation and higher birth weight warrants further investigation. This trial was registered at clinicaltrials.gov as NCT02244684.

scholarly journals Birthweight DNA methylation signatures in infant saliva

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Chiara Moccia ◽  
Maja Popovic ◽  
Elena Isaevska ◽  
Valentina Fiano ◽  
Morena Trevisan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Gestational Age ◽  
Low Birthweight ◽  
Continuous Variable ◽  
Linear Regression Models ◽  
Association Analyses ◽  
Cpg Sites ◽  
Adverse Health Outcomes ◽  
The Look

Abstract Background Low birthweight has been repeatedly associated with long-term adverse health outcomes and many non-communicable diseases. Our aim was to look-up cord blood birthweight-associated CpG sites identified by the PACE Consortium in infant saliva, and to explore saliva-specific DNA methylation signatures of birthweight. Methods DNA methylation was assessed using Infinium HumanMethylation450K array in 135 saliva samples collected from children of the NINFEA birth cohort at an average age of 10.8 (range 7–17) months. The association analyses between birthweight and DNA methylation variations were carried out using robust linear regression models both in the exploratory EWAS analyses and in the look-up of the PACE findings in infant saliva. Results None of the cord blood birthweight-associated CpGs identified by the PACE Consortium was associated with birthweight when analysed in infant saliva. In saliva EWAS analyses, considering a false discovery rate p-values < 0.05, birthweight as continuous variable was associated with DNA methylation in 44 CpG sites; being born small for gestational age (SGA, lower 10th percentile of birthweight for gestational age according to WHO reference charts) was associated with DNA methylation in 44 CpGs, with only one overlapping CpG between the two analyses. Despite no overlap with PACE results at the CpG level, two of the top saliva birthweight CpGs mapped at genes associated with birthweight with the same direction of the effect also in the PACE Consortium (MACROD1 and RPTOR). Conclusion Our study provides an indication of the birthweight and SGA epigenetic salivary signatures in children around 10 months of age. DNA methylation signatures in cord blood may not be comparable with saliva DNA methylation signatures at about 10 months of age, suggesting that the birthweight epigenetic marks are likely time and tissue specific.

scholarly journals Associations of circulating folate, vitamin B12 and homocysteine concentrations in early pregnancy and cord blood with epigenetic gestational age: the Generation R Study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Giulietta S. Monasso ◽  
Leanne K. Küpers ◽  
Vincent W. V. Jaddoe ◽  
Sandra G. Heil ◽  
Janine F. Felix
Keyword(s):  
Dna Methylation ◽  
Vitamin B12 ◽  
Cord Blood ◽  
Gestational Age ◽  
Fetal Development ◽  
Maternal Plasma ◽  
Plasma Homocysteine ◽  
Training Population ◽  
Epigenetic Aging ◽  
Pregnancy Dating

Abstract Background Circulating folate, vitamin B12 and homocysteine concentrations during fetal development have been associated with health outcomes in childhood. Changes in fetal DNA methylation may be an underlying mechanism. This may be reflected in altered epigenetic aging of the fetus, as compared to chronological aging. The difference between gestational age derived in clinical practice and gestational age predicted from neonatal DNA methylation data is referred to as gestational age acceleration. Differences in circulating folate, vitamin B12 and homocysteine concentrations during fetal development may be associated with gestational age acceleration. Results Up to 1346 newborns participating in the Generation R Study, a population-based prospective cohort study, had both cord blood DNA methylation data available and information on plasma folate, serum total and active B12 and plasma homocysteine concentrations, measured in early pregnancy and/or in cord blood. A subgroup of 380 newborns had mothers with optimal pregnancy dating based on a regular menstrual cycle and a known date of last menstrual period. For comparison, gestational age acceleration was calculated based the method of both Bohlin and Knight. In the total study population, which was more similar to Bohlin’s training population, one standard deviation score (SDS) higher maternal plasma homocysteine concentrations was nominally associated with positive gestational age acceleration [0.07 weeks, 95% confidence interval (CI) 0.02, 0.13] by Bohlin’s method. In the subgroup with pregnancy dating based on last menstrual period, the method that was also used in Knight’s training population, one SDS higher cord serum total and active B12 concentrations were nominally associated with negative gestational age acceleration [(− 0.16 weeks, 95% CI − 0.30, − 0.02) and (− 0.15 weeks, 95% CI − 0.29, − 0.01), respectively] by Knight’s method. Conclusions We found some evidence to support associations of higher maternal plasma homocysteine concentrations with positive gestational age acceleration, suggesting faster epigenetic than clinical gestational aging. Cord serum vitamin B12 concentrations may be associated with negative gestational age acceleration, indicating slower epigenetic than clinical gestational aging. Future studies could examine whether altered fetal epigenetic aging underlies the associations of circulating homocysteine and vitamin B12 blood concentrations during fetal development with long-term health outcomes.

scholarly journals Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

2018 ◽  
Vol 19 (10) ◽  
pp. 3106 ◽  
Author(s):  
Kuniyasu Soda
Keyword(s):  
Dna Methylation ◽  
Carbon Metabolism ◽  
Methylation Status ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Dna Methyltransferases ◽  
Polyamine Metabolism ◽  
Methyl Group ◽  
Wide Range ◽  
One Carbon Metabolism

Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed.

scholarly journals Association between one-carbon metabolism indices and DNA methylation status in maternal and cord blood

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Anna K. Knight ◽  
Hea Jin Park ◽  
Dorothy B. Hausman ◽  
Jennifer M. Fleming ◽  
Victoria L. Bland ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cord Blood ◽  
Carbon Metabolism ◽  
Methylation Status ◽  
One Carbon Metabolism

scholarly journals Cord blood buffy coat DNA methylation is comparable to whole cord blood methylation

2017 ◽  
Author(s):  
John Dou ◽  
Rebecca J. Schmidt ◽  
Kelly S. Benke ◽  
Craig Newschaffer ◽  
Irva Hertz-Picciotto ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Blood Cell ◽  
Cord Blood ◽  
Whole Blood ◽  
Cell Types ◽  
Buffy Coat ◽  
Sample Type ◽  
Blood Samples ◽  
Cell Composition ◽  
Cell Counts

AbstractBackgroundCord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells by generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability.ObjectivesTo evaluate differences in cell composition and DNA methylation between buffy coat and whole cord blood samples.MethodsCord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in 8 individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition.ResultsDNA methylation PCs were associated with individual (PPC1=1.4x10-9; PPC2=2.9x10-5; PPC3=3.8x10-5; PPC4=4.2x10-6; PPC5=9.9x10-13), and not with sample type (PPC1-5>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired individual samples ranged from r=0.66 to r=0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (5 sites had unadjusted P<10-5). Estimated cell type proportions did not differ by sample type (P=0.86), and estimated cell counts were highly correlated between paired samples (r=0.99).ConclusionsDifferences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.

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