A complex adaptive system in which environmental stress affects gene expression during development

Dental development is a complex adaptive system influenced by genetic-epigenetic-environmental factors. The mature dentition is a paradigm for general development and is an accessible, permanent record of interactions affecting development from 6 weeks in-utero to 20 years of age. Published research on the dentition of a large group of Romano-Britons has indicated that three major environmental insults acting throughout the developmental period are associated with high frequencies of dental variations. Based on those studies and the literature, the aetiological network incorporates the effects of excessive lead ingestion, poor nutrition and infections on the endocrine and immune systems, epigenome and gene expression. The environmental insults act independently and synergistically on both the endocrine and immune systems, which in turn have reciprocal interactions with each other, as well as on the epigenome. Thus, a complex subnetwork influences the epigenome and modifies one or more of three mechanisms by which it controls gene expression, that is, DNA methylation, post-translational histone modification and microRNA expression. The environmental-epigenetic-genetic interactions behave as a complex adaptive system that can be illustrated in a network diagram. The epigenetic modifications can have long-term health effects in the individual and some may also be heritable.