Intergenerational effects of maternal early life adversity on infant DNA methylation of NR3C1

2018 ◽  
Vol 28 (9) ◽  
pp. 656
Author(s):  
Katherine Bowers ◽  
Hong Ji ◽  
Lili Ding ◽  
Robert Ammerman ◽  
Judith Van Ginkel ◽  
...  
Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Golareh Agha ◽  
Andres E Houseman ◽  
Karl T Kelsey ◽  
Charles B Eaton ◽  
Stephen L Buka ◽  
...  

RATIONALE: Adiposity is a major cardiovascular risk factor, suggesting an important role for adipose tissue in development of cardiovascular outcomes. There is evidence that early life adversity has a lasting impact on the development of adiposity, particularly in women. In utero exposure to famine was related to adulthood adiposity in women but not men, and associations between early life socioeconomic adversity and adulthood adiposity is established in women but less so in men. There is interest in epigenetic mechanisms by which early life adversity may program risk for adiposity, and utilizing directly affected tissue such as adipose tissue is ideal for investigating such mechanisms. Objective: To determine whether prenatally-assessed socioeconomic index (SEI) is associated with adulthood genome-wide DNA methylation in blood and adipose tissue, and whether associations differ between men and women. Methods: Participants (aged 44-50 y) were from the New England Family Study birth cohort, born in Providence, RI. Of 400 participants assessed during 2010-2011, a representative subsample of 106 participants (68 women, 38 men) was selected for DNA methylation analyses. SEI was measured prenatally as a composite numerical score, using a weighted percentile of both parents’ educational attainment, occupation, and income relative to the US population. DNA methylation in subcutaneous adipose tissue and peripheral blood leukocytes was evaluated using the Infinium HumanMethylation450K BeadChip. Results: Prenatal SEI was associated with adipose tissue DNA methylation in women (permutation-based omnibus p-values <0.001), but not men or the pooled sample. Associations in women were not attenuated after adjustment for race, current smoking, or mother’s smoking during pregnancy. Prenatal SEI was not related to blood DNA methylation. Conclusion: Results provide mechanistic insight on the association between early life adversity and adulthood adiposity, which is seen mainly in women.


2016 ◽  
Vol 28 (4pt2) ◽  
pp. 1259-1272 ◽  
Author(s):  
Renaud Massart ◽  
Zsofia Nemoda ◽  
Matthew J. Suderman ◽  
Sheila Sutti ◽  
Angela M. Ruggiero ◽  
...  

AbstractStudies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex.


2019 ◽  
Author(s):  
Matthew N. Zipple ◽  
Elizabeth A. Archie ◽  
Jenny Tung ◽  
Jeanne Altmann ◽  
Susan C. Alberts

AbstractIn humans and nonhuman animals, early life adversity can affect an individual’s health, survival, and fertility for many years after the adverse experience. However, whether early life adversity also imposes intergenerational effects on the exposed individual’s offspring is not well understood. Here, we fill this gap by leveraging prospective, longitudinal data on a wild, long-lived primate. We find that juveniles whose mothers experienced early life adversity exhibit high mortality before age 4, and this effect is independent of the juvenile’s own experience of early adversity. Furthermore, our results point towards a strong role for classic parental effects in driving these effects: mothers that experienced early life adversity displayed reduced viability in adulthood, which in turn led to reductions in offspring survival. Importantly, these mothers’ juvenile offspring often preceded them in death by 1 to 2 years, indicating that, for high adversity mothers, the quality of maternal care declines near the end of life. While we cannot exclude direct effects of a parent’s environment on offspring quality (e.g., transgenerational epigenetic changes), our results are most consistent with a classic parental effect, in which the environment experienced by a parent affects its future phenotype and therefore its offspring’s phenotype. Together, our findings demonstrate that adversity experienced by individuals in one generation can have strong effects on the survival of offspring in the next generation, even if those offspring did not themselves experience early adversity.


2019 ◽  
Vol 29 ◽  
pp. S8
Author(s):  
E. Dunn ◽  
Y. Zhu ◽  
A. Simpkin ◽  
M. Suderman ◽  
E. Walton ◽  
...  

2017 ◽  
Vol 41 (S1) ◽  
pp. S19-S20 ◽  
Author(s):  
T. Frodl ◽  
L. Tozzi ◽  
C. Farrell ◽  
K. Doolin ◽  
V. O’Keane ◽  
...  

IntroductionMajor depressive disorder (MDD) is a common psychiatric condition, affecting up to 350 million people worldwide. Its pathogenesis seems to involve dysregulation of the hypothalamic-pituitary (HPA) axis and inflammation as key elements of the condition. Stressful life events and in particular early life adversity seem to play an important role as risk factors for MDD. Epigenetic, which has been found to impact in the transcription of genes, seem to be associated with brain structure and function. Aim of the research was to provide an overview about neuroimaging (epi)-genetics in MDD.MethodsFunctional MRI, epigenetic and genetic information was obtained in a cohort of patients with MDD and healthy controls. Associations between, early life adversity, methylation of FKBP5 and SLC6A4, genetic variants and brain function and connectivity have been analysed.ResultsHigher methylation of SLC6A4 gene was associated with higher BOLD response during emotion processing and lower BOLD response during higher order cognitive processes. Healthy participants with higher SLC6A4 methylation involved prefrontal cortical regions to a greater extent than the participants with lower SLC6A4 methylation, when trying to switch attention away from negative emotional stimuli (Frodl et al., 2015). Moreover, FKBP5 methylation was association with HPA axis functioning and amygdala brain function in patients with MDD. FKBP5 methylation also was related to grey matter volume.ConclusionsOur study provides further support to the hypothesis that DNA methylation plays a role. Particular peripheral DNA methylation states of MDD candidate genes are associated with brain function during emotion processing in patients with MDD.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2018 ◽  
Author(s):  
Shan Jiang ◽  
Noriko Kamei ◽  
Jessica L. Bolton ◽  
Xinyi Ma ◽  
Hal S. Stern ◽  
...  

AbstractGenetic and environmental factors interact during sensitive periods early in life to influence mental health and disease via epigenetic processes such as DNA methylation. However, it is not known if DNA methylation changes outside the brain provide an ‘epigenetic signature’ of early-life experiences. Here, we employed a novel intra-individual approach by testing DNA methylation from buccal cells of individual rats before and immediately after exposure to one week of typical or adverse life experience. We find that whereas inter-individual changes in DNA methylation reflect the effect of age, DNA methylation changes within paired DNA samples from the same individual reflect the impact of diverse neonatal experiences. Genes coding for critical cellular–metabolic enzymes, ion channels and receptors were more methylated in pups exposed to the adverse environment, predictive of their repression. In contrast, the adverse experience was associated with less methylation on genes involved in pathways of death and inflammation as well as cell-fate related transcription factors, indicating their potential upregulation. Thus, intra-individual methylome signatures indicate large-scale transcription-driven alterations of cellular fate, growth and function.


2020 ◽  
Author(s):  
Sam K Patterson ◽  
Katie Hinde ◽  
Angela B Bond ◽  
Benjamin C Trumble ◽  
Shirley C Strum ◽  
...  

Adverse experiences during early life exert important effects on development, health, reproduction, and social bonds, with consequences often persisting across generations. A mother's early life experiences can impact her offspring's development through a number of pathways, such as maternal care, physiological signaling through glucocorticoids, or even intergenerational effects like epigenetic inheritance. Early life adversity in female yellow baboons (Papio cynocephalus) predicts elevated glucocorticoids, reduced sociality, shortened lifespan, and higher offspring mortality. If baboon mothers with more early life adversity, experience poorer condition and struggle to provide for their offspring, this could contribute to the persisting transgenerational effects of adversity. Here, we examined the effects of mothers' early life adversity on their maternal effort, physiology, and offspring survivability in a population of olive baboons, Papio anubis. Mothers who experienced more adversity in their own early development exerted greater maternal effort (i.e., spent more time nursing and carrying) and had higher glucocorticoid metabolites than mothers with less early life adversity. Offspring of mothers with more early life adversity had reduced survivability compared to offspring of mothers with less early life adversity. There was no evidence that high maternal social rank buffered against the effects of early life adversity. Our data suggest early life experiences can have lasting consequences on maternal effort and physiology, which may function as proximate mechanisms for intergenerational effects of maternal experience.


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