Environmental Epigenetic Changes, as Risk Factors for the Development of Diseases in Children: A Systematic Review

Abstract

Background: Children are susceptible to environmental contaminants and are at risk of developing diseases, more so if the exposure begins at an early age. Epidemiological studies have postulated the hypothesis of the fetal origin of disease, which is mediated by epigenetic changes. Epigenetic marks are inheritable; they modulate the gene expression and can affect human health due to the presence of environmental factors.

Objective: This review focuses on DNA-methylation and its association with environmental-related diseases in children.

Methods: A search for studies related to DNA-methylation in children by pre- or post-natal environmental exposures was conducted, and those studies with appropriate designs and statistical analyses and evaluations of the exposure were selected.

Findings: Prenatal and early life environmental factors, from diet to exposure to pollutants, have been associated with epigenetic changes, specifically DNA-methylation. Thus, maternal nutrition and smoking and exposure to air particulate matter, polycyclic aromatic hydrocarbons, arsenic, heavy metals, persistent organic pollutants, and some endocrine disrupters during pregnancy have been associated with genomic and gene-specific newborns' DNA-methylation changes that have shown in some cases sex-specific patterns. In addition, these maternal factors may deregulate the placental DNA-methylation balance and could induce a fetal reprogramming and later-in-life diseases.

Conclusions: Exposure to environmental pollutants during prenatal and early life can trigger epigenetic imbalances and eventually the development of diseases in children. The integration of epigenetic data should be considered in future risk assessments.

Figure 1

Susceptibility windows of DNA-methylation due to environmental pollutants. The epigenome undergoes reprogramming at two relevant stages, the gametogenesis and the early embryo preimplantation representing vulnerable stages to enviornemental exposures. During gametogenesis and fertilization, a general demethylation followed by a re-methylation process occur, with the exception of imprinted genes. DNA-methylation patterns are reestablished by DNA methyl-transferases DNMT3a and DNMT3b [1]. 5 mC, 5-methylcytosine. BPA, bisphenol A. Cd, cadmium. As arsenic. Pb, lead. Hg, mercury.