Introduction

Other chapters in this volume address the possibilities that maternal gestational weight gain, maternal obesity, and gestational diabetes influence the risk of obesity in the developing offspring through adverse influences of the intrauterine environment during periods of developmental plasticity. In this chapter we review the literature, which suggests that epigenetic modulation of gene expression is likely to serve as one of the more promiscuous molecular mechanisms with which these maternal and early developmental footprints are cast. Together with other potential mechanisms (e.g., establishment and perturbation of the microbiome) layered epigenomic regulation, genomic instability, and molecular and developmental biology are altering our understanding as to how the developmental origins of obesity and associated metabolic disease take their roots.

Epigenetic modifications and the developmental origins of health and disease

While genomic DNA is the template of our heredity, it is the coordination and regulation of its expression that results in the wide complexity and diversity seen among organisms. In the “postgenomic era,” investigators have begun to appreciate higher order architectural features of the genome, which include not only single nucleotide variance in gene regulatory regions (e.g., single nucleotide polymorphisms, or SNPs), but also genomic structural variation (i.e., copy number imbalance through large insertions or deletions). Collectively, structural rearrangements acting in concert with allelic polymorphisms contribute to the genomic landscape from which disease phenotypes arise.