Prenatal Air Pollution Exposure and Placental DNA Methylation Changes: Implications on Fetal Development and Future Disease Susceptibility

The Developmental Origins of Health and Disease (DOHaD) concept postulates that in utero exposures influence fetal programming and health in later life. Throughout pregnancy, the placenta plays a central role in fetal programming; it regulates the in utero environment and acts as a gatekeeper for nutrient and waste exchange between the mother and the fetus. Maternal exposure to air pollution, including heavy metals, can reach the placenta, where they alter DNA methylation patterns, leading to changes in placental function and fetal reprogramming. This review explores the current knowledge on placental DNA methylation changes associated with prenatal air pollution (including heavy metals) exposure and highlights its effects on fetal development and disease susceptibility. Prenatal exposure to air pollution and heavy metals was associated with altered placental DNA methylation at the global and promoter regions of genes involved in biological processes such as energy metabolism, circadian rhythm, DNA repair, inflammation, cell differentiation, and organ development. The altered placental methylation of these genes was, in some studies, associated with adverse birth outcomes such as low birth weight, small for gestational age, and decreased head circumference. Moreover, few studies indicate that DNA methylation changes in the placenta were sex-specific, and infants born with altered placental DNA methylation patterns were predisposed to developing neurobehavioral abnormalities, cancer, and atopic dermatitis. These findings highlight the importance of more effective and stricter environmental and public health policies to reduce air pollution and protect human health.

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106 The Effects of Fetal Programming on Offspring Pancreas DNA Methylation

Journal of Animal Science ◽

10.1093/jas/skab235.097 ◽

2021 ◽

Vol 99 (Supplement_3) ◽

pp. 54-55

Author(s):

Maria L Hoffman

Keyword(s):

Dna Methylation ◽

Fetal Programming ◽

Maternal Nutrition ◽

Maternal Diet ◽

Multiple Generations ◽

Livestock Species ◽

Maternal Programming ◽

Genome Bisulfite Sequencing ◽

The Many ◽

Methylation Patterns

Abstract It has been well documented that fetal programming, caused by changes to the maternal environment during pregnancy, can impact the overall health and growth of the offspring in livestock and non-livestock species alike. These effects are observed in the F1 offspring as well as across subsequent generations; however, the mechanisms by which this occurs are still poorly understood. Epigenetics is one of the many mechanisms that is hypothesized to have a role in fetal programming and may be mediating the observed effects across multiple generations. It has been demonstrated by others that DNA methylation patterns can be altered by an individuals’ diet and that the pancreas is vulnerable to the effects of fetal programming. Therefore, we evaluated the effects of poor maternal nutrition during gestation on the pancreas tissue of lambs. We have demonstrated that maternal under- or overnutrition during gestation alters the DNA methylation patterns of the offspring pancreas tissue with these effects being diet dependent and sex specific. We have also begun evaluating the effects of maternal diet in murine models using whole-genome bisulfite sequencing to compare species differences and determine if there are any changes conserved across species. This will allow us to focus on a smaller number of critical factors in individuals as they age and across multiple generations in livestock species such as sheep and cattle. From these data we will be able to elucidate the role DNA methylation has in mediating the effects of maternal programming in the pancreas tissue.

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Exposure to Maternal Diabetes in Utero and DNA Methylation Patterns in the Offspring

Immunometabolism ◽

10.2478/immun-2013-0001 ◽

2013 ◽

Vol 1 ◽

pp. 1-9 ◽

Cited By ~ 41

Author(s):

Nancy A West ◽

Katerina Kechris ◽

Dana Dabelea

Keyword(s):

Dna Methylation ◽

Maternal Diabetes ◽

In Utero ◽

Methylation Patterns

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What is the evidence in humans that DNA methylation changes link events in utero and later life disease?

Clinical Endocrinology ◽

10.1111/cen.12164 ◽

2013 ◽

Vol 78 (6) ◽

pp. 814-822 ◽

Cited By ~ 48

Author(s):

Rebecca M. Reynolds ◽

Greta H. Jacobsen ◽

Amanda J. Drake

Keyword(s):

Dna Methylation ◽

Later Life ◽

In Utero

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Reprogramming of miR-181a/DNA methylation patterns contribute to the maternal nicotine exposure-induced fetal programming of cardiac ischemia-sensitive phenotype in postnatal life

Theranostics ◽

10.7150/thno.48297 ◽

2020 ◽

Vol 10 (25) ◽

pp. 11820-11836

Author(s):

Jie Jian ◽

Peng Zhang ◽

Yong Li ◽

Bailin Liu ◽

Yanyan Zhang ◽

...

Keyword(s):

Dna Methylation ◽

Fetal Programming ◽

Cardiac Ischemia ◽

Postnatal Life ◽

Nicotine Exposure ◽

Methylation Patterns

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Mitochondrial DNA content and DNA methylation in association with exposure to particulate air pollution during critical periods of in utero life

ISEE Conference Abstracts ◽

10.1289/isee.2013.s-3-06-02 ◽

2013 ◽

Vol 2013 (1) ◽

pp. 5814

Author(s):

Tim S. Nawrot

Keyword(s):

Dna Methylation ◽

Air Pollution ◽

Mitochondrial Dna ◽

Dna Content ◽

In Utero ◽

Critical Periods ◽

Particulate Air Pollution ◽

Mitochondrial Dna Content

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Methionine metabolism in Yucatan miniature swine

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2016-0158 ◽

2016 ◽

Vol 41 (6) ◽

pp. 691-691 ◽

Cited By ~ 2

Author(s):

Laura E. McBreairty

Keyword(s):

Dna Methylation ◽

Supply And Demand ◽

Later Life ◽

In Utero ◽

Methionine Metabolism ◽

Miniature Swine ◽

Methyl Group ◽

Epigenetic Patterns ◽

Poor Nutrition ◽

Lower Capacity

Methionine is an essential amino acid which when not incorporated into protein, can be converted to S-adenosylmethionine, the universal methyl donor in over 200 transmethylation reactions, which include creatine and phosphatidylcholine (PC) synthesis, as well as deoxyribonucleic acid (DNA) methylation. Following transmethylation, homocysteine is formed, which can be converted to cysteine via transsulfuration or remethylated to methionine by receiving a methyl group from folate or betaine. Changes to methyl group availability in utero can lead to permanent changes in epigenetic patterns of DNA methylation, which has been implicated in “fetal programming”, a phenomenon associated with poor nutrition during fetal development that results in low birth weight and disease in later life. It has been shown that programming can also occur in the neonate. Our global objective was to understand how the variability of nutrients involved in methionine metabolism can affect methionine and methyl group availability. We hypothesize that nutrients that converge on methionine metabolism can affect methionine availability for its various functions. In this thesis, we used intrauterine growth restricted (IUGR) piglets to investigate whether a global nutritional insult in utero can lead to a perturbed methionine metabolism. Our results demonstrate that IUGR piglets have a lower capacity to dispose of homocysteine via both transsulfuration and remethylation pathways, as well as a lower incorporation of methyl groups into PC. The second objective of this thesis was to determine whether variation in methionine supply and demand can affect methionine availability. We demonstrated that stimulating either acute or chronic creatine synthesis leads to lower methyl incorporation into protein and PC in pigs. Furthermore, when methionine is limiting, supplementation with either folate or betaine leads to higher methionine availability for protein synthesis. Finally, because creatine is increasingly being utilized as an ergogenic and neuroprotective supplement, we wanted to determine whether provision of the creatine precursor, guanidinoacetate (GAA), could effectively increase tissue creatine stores. We showed that 2.5 weeks of supplementation with GAA is more effective than creatine at increasing hepatic and muscle creatine stores. The results of this thesis demonstrate that the presence of IUGR, an increased demand for creatine synthesis, or the supplementation with remethylation nutrients can each affect methionine availability; all are important when considering neonatal nutrient requirements. Furthermore, although GAA is effective at increasing levels of tissue creatine, higher GAA methylation can limit methionine availability for growth and synthesis of PC.

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Nutrition during Pregnancy Impacts Offspring's Epigenetic Status—Evidence from Human and Animal Studies

Nutrition and Metabolic Insights ◽

10.4137/nmi.s29527 ◽

2015 ◽

Vol 8s1 ◽

pp. NMI.S29527 ◽

Cited By ~ 14

Author(s):

Aisling A. Geraghty ◽

Karen L. Lindsay ◽

Goiuri Alberdi ◽

Fionnuala M. McAuliffe ◽

Eileen R. Gibney

Keyword(s):

Dna Methylation ◽

Growth And Development ◽

Critical Period ◽

Animal Studies ◽

Maternal Nutrition ◽

Later Life ◽

Future Health ◽

Global Methylation ◽

Methyl Donors ◽

Methylation Patterns

Pregnancy is a vital time of growth and development during which maternal nutrition significantly influences the future health of both mother and baby. During pregnancy, the fetus experiences a critical period of plasticity. Epigenetics, specifically DNA methylation, plays an important role here. As nutrition is influential for DNA methylation, this review aims to determine if maternal nutrition during pregnancy can modify the offspring's epigenome at birth. Research focuses on micronutrients and methyl donors such as folate and B vitamins. Evidence suggests that maternal nutrition does not largely influence global methylation patterns, particularly in nutrient-replete populations; however, an important impact on gene-specific methylation is observed. A link is shown between maternal nutrition and the methylome of the offspring; however, there remains a paucity of research. With the potential to use DNA methylation patterns at birth to predict health of the child in later life, it is vital that further research be carried out.

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DNMTs and Impact of CpG Content, Transcription Factors, Consensus Motifs, lncRNAs, and Histone Marks on DNA Methylation

Genes ◽

10.3390/genes11111336 ◽

2020 ◽

Vol 11 (11) ◽

pp. 1336 ◽

Cited By ~ 1

Author(s):

Jaqueline Loaeza-Loaeza ◽

Adriana S. Beltran ◽

Daniel Hernández-Sotelo

Keyword(s):

Dna Methylation ◽

Transcriptional Regulation ◽

Transcription Factors ◽

Current Knowledge ◽

Dna Methyltransferases ◽

Histone Marks ◽

Spatiotemporal Regulation ◽

Genome Wide ◽

Health And Disease ◽

Methylation Patterns

DNA methyltransferases (DNMTs) play an essential role in DNA methylation and transcriptional regulation in the genome. DNMTs, along with other poorly studied elements, modulate the dynamic DNA methylation patterns of embryonic and adult cells. We summarize the current knowledge on the molecular mechanism of DNMTs’ functional targeting to maintain genome-wide DNA methylation patterns. We focus on DNMTs’ intrinsic characteristics, transcriptional regulation, and post-transcriptional modifications. Furthermore, we focus special attention on the DNMTs’ specificity for target sites, including key cis-regulatory factors such as CpG content, common motifs, transcription factors (TF) binding sites, lncRNAs, and histone marks to regulate DNA methylation. We also review how complexes of DNMTs/TFs or DNMTs/lncRNAs are involved in DNA methylation in specific genome regions. Understanding these processes is essential because the spatiotemporal regulation of DNA methylation modulates gene expression in health and disease.

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