Epigenetics and DOHaD: from basics to birth and beyond

Abstract

Developmental origins of health and disease (DOHaD) is the study of how the early life environment can impact the risk of chronic diseases from childhood to adulthood and the mechanisms involved. Epigenetic modifications such as DNA methylation, histone modifications and non-coding RNAs are involved in mediating how early life environment impacts later health. This review is a summary of the Epigenetics and DOHaD workshop held at the 2016 DOHaD Society of Australia and New Zealand Conference. Our extensive knowledge of how the early life environment impacts later risk for chronic disease would not have been possible without animal models. In this review we highlight some animal model examples that demonstrate how an adverse early life exposure results in epigenetic and gene expression changes that may contribute to increased risk of chronic disease later in life. Type 2 diabetes and cardiovascular disease are chronic diseases with an increasing incidence due to the increased number of children and adults that are obese. Epigenetic changes such as DNA methylation have been shown to be associated with metabolic health measures and potentially predict future metabolic health status. Although more difficult to elucidate in humans, recent studies suggest that DNA methylation may be one of the epigenetic mechanisms that mediates the effects of early life exposures on later life risk of obesity and obesity related diseases. Finally, we discuss the role of the microbiome and how it is a new player in developmental programming and mediating early life exposures on later risk of chronic disease.

Maternal levels of endocrine disrupting chemicals in the first trimester of pregnancy are associated with infant cord blood DNA methylation

“…Recently, considerable emphasis has been placed on determining the contribution of early life exposures to the rising tide of obesity [44]. However, there have been few epidemiological studies focused on assessing the epigenetic impact of exposures to EDCs in early pregnancy within the context of growth and metabolic programming.…”

Developmental Dieldrin Exposure Alters DNA Methylation at Genes Related to Dopaminergic Neuron Development and Parkinson’s Disease in Mouse Midbrain

“…Such a model fits into the developmental origins of health and disease (DOHaD) paradigm, which holds that early-life environmental exposures modify disease risk into adulthood (Heindel and Vandenberg, 2015). Under this paradigm, the epigenome is a mechanism by which gene regulation is developmentally programmed to respond to later-life perturbations (Bianco-Miotto et al, 2017;Gluckman et al, 2008). When considering our results from a DOHaD perspective, it makes sense that a developmental exposure could produce clear epigenetic changes without associated changes in gene expression.…”

Body Mass Index and Cardiovascular Risk Factors in Children and Adolescents with High Birth Weight

“…Based on concepts of the Developmental Origins of Health and Disease Hypothesis, diseases or stimuli in early stages of life can lead to changes in physiology, structure, and functioning of organs and systems, with long-term repercussions [1]. Thus, low birth weight (LBW; <2,500 g) and high birth weight (HBW; ≥4,000 g) are associated with a higher risk of developing chronic non-communicable diseases [2].…”