scholarly journals DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease?

2012 ◽  
Vol 5 (1) ◽  
Author(s):  
Nahid Turan ◽  
Mohamed F Ghalwash ◽  
Sunita Katari ◽  
Christos Coutifaris ◽  
Zoran Obradovic ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Molecular Signature ◽  
Developmental Origins ◽  
Adult Disease

Birth weights smaller or larger than the placenta predict BMI and blood pressure at age 7 years

2010 ◽  
Vol 1 (2) ◽  
pp. 123-130 ◽  
Author(s):  
D. P. Misra ◽  
C. M. Salafia ◽  
A. K. Charles ◽  
R. K. Miller
Keyword(s):  
Blood Pressure ◽  
African American ◽  
Birth Weight ◽  
Developmental Origins ◽  
Adult Disease ◽  
Unit Increase ◽  
Independent Variable ◽  
American Children ◽  
African American Race ◽  
Insight Into

We hypothesized that the altered placental proportions that influence birth weight affect childhood body proportions, and that these effects would be independent of birth weight. We also hypothesized that altered placental proportions might affect the fetal cardiovascular system, and may be reflected in variation in childhood blood pressure. By using linear regression with birth weight as the dependent variable, placental variables were entered as predictors. The predicted birth weights based on placental factors were then obtained. The ratio of the actual birth weight to that predicted by placental parameters (observed/expected ratio, OER) was used as the independent variable in analyses of age 7 year body mass index (BMI) and diastolic blood pressure (DBP) in the 15,902 singleton liveborns delivered between 34 and 43 weeks. The standardized residual birth weight was also used as a variable to examine the effects of birth weight that is not consistent with placental parameters. For each unit increase in the OER, BMI at 7 years increased 1 kg/m2 (P < 0.0001). The OER also had a significant effect on DBP (β = 4.52, P < 0.001) at 7 years of age but only among African-American children. Results for the standardized residual birth weight variable were consistent with the OER. All results were adjusted for gestational age, sex, socioeconomic status, African-American race and maternal pre-pregnancy BMI. Being larger or smaller than predicted by one’s placenta affects childhood body composition and blood pressure. The placental measurements provide insight into pathophysiological mechanisms of the developmental origins of adult disease.

scholarly journals Invited Commentary: Is DNA Methylation an Actionable Mediator of Prenatal Exposure Effects on Child Health?

2019 ◽  
Vol 188 (11) ◽  
pp. 1887-1889 ◽  
Author(s):  
Christine Ladd-Acosta ◽  
M Daniele Fallin
Keyword(s):  
Dna Methylation ◽  
Birth Weight ◽  
Repeated Measures ◽  
Ethnically Diverse ◽  
Molecular Signature ◽  
Prenatal Smoking ◽  
Mediation Analyses ◽  
Adverse Health Outcomes ◽  
Smoking Exposure ◽  
The Impact

Abstract A substantial body of literature has shown robust associations between prenatal smoking exposure and DNA methylation levels. The pattern of DNA methylation can be used as a molecular signature of past prenatal smoking exposure and might also provide mechanistic insights into associations between prenatal smoking exposure and adverse health outcomes. In this issue of the Journal, Cardenas et al. (Am J Epidemiol. 2019;188(11):1878–1886) evaluated whether DNA methylation mediates the association between prenatal smoking and low birth weight in a tissue that is mechanistically relevant to birth weight—the placenta—using formal mediation analyses. They found that methylation levels, at 5 loci, mediated smoking exposure effects on birth weight but only among children whose mothers smoked during pregnancy. Given the use of formal mediation methods and measurement in a mechanistically relevant tissue, this work has the potential to inform novel directions for intervention. Replication of these findings in larger and more racially and ethnically diverse samples, repeated measures to better tease apart the timing of DNA methylation changes with respect to exposure and birth weight, and continued use of intervention-focused mediation methods are needed before the impact of these findings will be fully realized.

scholarly journals Genome-wide associations for birth weight and correlations with adult disease

Nature ◽  
2016 ◽  
Vol 538 (7624) ◽  
pp. 248-252 ◽  
Author(s):  
Momoko Horikoshi ◽  
◽  
Robin N. Beaumont ◽  
Felix R. Day ◽  
Nicole M. Warrington ◽  
...  
Keyword(s):  
Birth Weight ◽  
Adult Disease ◽  
Genome Wide

Epigenetic Mechanisms in the Developmental Origins of Adult Disease

2011 ◽  
pp. 187-204 ◽  
Author(s):  
Keith M. Godfrey ◽  
Karen A. Lillycrop ◽  
Mark A. Hanson ◽  
Graham C. Burdge
Keyword(s):  
Epigenetic Mechanisms ◽  
Developmental Origins ◽  
Adult Disease

scholarly journals Homage to the ‘H’ in developmental origins of health and disease

2016 ◽  
Vol 8 (1) ◽  
pp. 8-29 ◽  
Author(s):  
C. S. Rosenfeld
Keyword(s):  
Female Offspring ◽  
Postnatal Period ◽  
Environmental Chemicals ◽  
Primary Concern ◽  
Developmental Origins ◽  
Adult Health ◽  
Fetal Origins ◽  
Adult Disease ◽  
Remediation Strategies ◽  
Health And Disease

Abundant evidence exists linking maternal and paternal environments from pericopconception through the postnatal period to later risk to offspring diseases. This concept was first articulated by the late Sir David Barker and as such coined the Barker Hypothesis. The term was then mutated to Fetal Origins of Adult Disease and finally broadened to developmental origins of adult health and disease (DOHaD) in recognition that the perinatal environment can shape both health and disease in resulting offspring. Developmental exposure to various factors, including stress, obesity, caloric-rich diets and environmental chemicals can lead to detrimental offspring health outcomes. However, less attention has been paid to date on measures that parents can take to promote the long-term health of their offspring. In essence, have we neglected to consider the ‘H’ in DOHaD? It is the ‘H’ component that should be of primary concern to expecting mothers and fathers and those seeking to have children. While it may not be possible to eliminate exposure to all pernicious factors, prevention/remediation strategies may tip the scale to health rather than disease. By understanding disruptive DOHaD mechanisms, it may also illuminate behavioral modifications that parents can adapt before fertilization and throughout the neonatal period to promote the lifelong health of their male and female offspring. Three possibilities will be explored in the current review: parental exercise, probiotic supplementation and breastfeeding in the case of mothers. The ‘H’ paradigm should be the focus going forward as a healthy start can indeed last a lifetime.

Abstract 500: DNA Methylation Profiling Reveals an Epithelial/Endothelial-Mesenchymal Transition-like Signature of Intima-Media Cells in the Ascending Aorta of Bicuspid Aortic Valve Patients

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Hanna M Björck ◽  
Lei Du ◽  
Valentina Paloschi ◽  
Shohreh Maleki ◽  
Silvia Pulignani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Epithelial Mesenchymal Transition ◽  
Ascending Aorta ◽  
Molecular Signature ◽  
Aortic Valves ◽  
Global Methylation ◽  
Mesenchymal Transition ◽  
Differentially Methylated Genes ◽  
Increased Risk

Introduction: Individuals with bicuspid aortic valves (BAV) are at increased risk of ascending aortic aneurysm than individuals with tricuspid aortic valves (TAV), but the underlying mechanism is not fully understood. Aberrant DNA methylation has been described in various human diseases, and we have shown that key enzymes in the methylation machinery are differentially expressed in the aortic intima-media of BAV and TAV patients. In the present study, we assessed the hypothesis that DNA methylation may play an important role during aneurysm formation in BAV. We undertook a global methylation approach to delineate biological processes associated with BAV aortopathy, using TAV as a reference. Methods: Ascending aortic biopsies were collected from 21 BAV and 24 TAV patients, with either a non-dilated or a dilated aorta, at the time of surgery. Global DNA methylation was measured in the intima-media layer using Illumina 450k Array. Gene expression was analyzed in the same samples using Affymetrix Exon Array. Results: Compared with TAV, the BAV dilated aorta was hypomethylated (P=0.031), correlating with an up-regulation of global gene expression. A total of 4913 differentially methylated regions (DMRs) were identified and Hallmark analysis of the DMR-associated genes with a fold change of 10% (n=3147) showed a gene signature of Epithelial Mesenchymal Transition (EMT) (FDR q=2.91e-29). This was further confirmed by functional annotation analysis of hypomethylated DMRs using the Genomic Regions Enrichment of Annotations Tool (Stanford University), showing association to actin filament bundle (P=7.09e-12), stress fibers (P=1.72e-11) and adherence junctions (P=2.97e-8). Interestingly, analysis of non-dilated BAV and TAV aorta revealed that genes involved in EMT were the most differentially methylated genes prior to dilatation (FDR q=1.18e-6). We further confirmed the EMT-related molecular signature by immunostaining of some key players of EMT. In conclusion, epigenetic profiling clearly revealed differential methylation between BAV and TAV aorta, particularly in EMT-related genes. Aberrant EMT in the ascending aorta prior to dilatation may constitute the basis for the increased aneurysm susceptibility in BAV patients.

Abstract P055: Adverse Early Life Exposures and Carotid Atherosclerosis in Midlife: LEAP study

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Charles B Eaton ◽  
Jennifer Maccani ◽  
Golareh Agha ◽  
Matthew Allison ◽  
Mary Roberts ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Birth Weight ◽  
Early Life ◽  
Carotid Plaque ◽  
Carotid Arteries ◽  
Carotid Atherosclerosis ◽  
Developmental Origins ◽  
Carotid Imt ◽  
Infancy And Early Childhood ◽  
Early Life Exposures

Background: The developmental origins hypothesis suggests that adverse early life exposures predispose individuals to the development of chronic disease later in life. We tested this hypothesis by evaluating prenatal, birth, infancy and early childhood factors as predictors of midlife carotid intimal thickness and presence of atherosclerotic plaque in the carotid arteries. Methods: Participants were from the New England Family Study (N= 371), over-sampled for racial/ethnic minorities and small/large size for gestational age at birth, who had carotid IMT assessed in 2010-2011. Socioeconomic position (SEP) was prospectively measured prenatally and at age 7. Self-reported maternal pre-pregnancy BMI, birth weight, placental weight and gestational age, Growth velocity (change in weight from birth to age 4 months), BMI and blood pressure at the age 7 were measured. At midlife carotid IMT(cIMT)was measured at three angles of the far wall of the common segment for both carotid arteries; the mean of maximum measurement for these 6 segments was determined, as well as presence of plaque. Results: Of the 371 middle aged (44-51 years) participants, 56% were women and 65% were white. After adjusting for age, gender and race, robust statistically significant associations with carotid IMT and carotid plaque were found for placental weight and BMI at age 7. Socioeconomic position at age 7 was associated cIMT while the association with carotid plaque was of borderline significance. Maternal pre-pregnancy BMI and systolic blood pressure (SBP) were marginally associated with the presence of any plaque in the offspring, while cIMT was not significantly associated. Early growth velocity was marginally associated with plaque but not cIMT and birth weight was not associated with either cIMT or plaque. Conclusion: This study provides some evidence to support the developmental origins hypothesis during the prenatal period, infancy and early childhood predicting carotid atherosclerosis in mid life.

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