The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

Abstract

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders.

Beyond the HPA-axis: Exploring maternal prenatal influences on birth outcomes and stress reactivity

“…Whether directly transferred through the placenta or indirectly affecting the fetal development through placental inflammation, elevated cytokines are hypothesized to act at multiple levels of the fetal brain, affecting neurogenesis, gliogenesis and the neurotransmitter systems (reviewed in Rakers et al, 2017). An alternative mechanism is that epigenetic mechanisms could mediate the impact of prenatal maternal inflammation on fetal brain development with potentially long-lasting effects as suggested by results of animal studies (Kundakovic & Jaric, 2017). Future efforts are needed to elucidate the role of maternal IL-6 levels in influencing rates of fetal growth and brain development in humans.…”

Emerging Genetic and Epigenetic Mechanisms Underlying Pubertal Maturation in Adolescence

“…affect neural circuit developmental pathways. Epigenetic landscape analysis (genome‐wide epigenetic modification quantitation) is a powerful tool that researchers are just now starting to use in order to predict or “read” developmental patterns and how they are affected by the environment (Kundakovic & Jaric, ; Orozco‐Solis & Sassone‐Corsi, ; Snigdha et al., ).…”

Methylmercury Epigenetics

“…There is a well-defined epigenetic association between prenatal environmental exposures and adverse neurodevelopmental outcomes [8]. As MeHg can cross the placental barrier [9], characteristic neurobehavioral deficits observed resultant to exposure [10][11][12] might have epigenetic foundations.…”