The early environment during development is emerging as a strong predictor of phenotype and disease in later life. When and how does the environment alter these later life outcomes? The “developmental origins of adult disease” hypothesis posits gene-environment interactions that result in long-lasting effects and suggests epigenetic inheritance as a prime mechanism.1
These early environmental influences can be dietary (total caloric intake, specific nutrient level, phytochemicals), physical (behavior, temperature, species density, stress), chemical (toxins, endocrine disruptors, pharmaceuticals) or unknown (stochastic, random effects). Traditionally, epigenetics has been defined as changes in gene expression in the absence of underlying changes in genetic information. More recent, refinement in the usage of the term specifies that epigenetic changes must be heritable from cell to cell, hence through cell lineage development or even transgenerationally from parent to offspring to grand-offspring.2
Thus, the convergence of evolutionary developmental biology, environmental toxicology and epigenetics is particularly important at the earliest stages of development when epigenetic modifications, such as DNA methylation, are the most sensitive to perturbation resulting in lifelong and possibly transgenerational effects.
The importance of early environment influences in modifying developmental trajectory has a long and colorful history leading from Jean-Baptiste Lamarck's idea that use of a body part would cause a heritable increase in the size of that body part.3
His proposed mechanism was that organisms have a “tendency to progression” and that offspring can inherit traits acquired by the habits of the parents.4
Early environmental manipulations were tried by discredited Soviet biologist Trofim Lysenko in his claims that crops could be adapted to cold climates by exposing seeds to cold temperatures.5
This culminated in his attempts at feeding special diets to gestating cattle hybrids to produce offspring with greater milk productivity.6
Such misconceptions persisted despite early refutations such as August Weismann's experiment in cutting the tails off of rats over five generations while never observing the birth of a tailless rat.7
He explicitly refuted the idea of soft inheritance by proposing what is now called the “Weismann barrier,” stating that germ cells cannot inherit modifications acquired by the body. More recent studies, however, have shown that with an understanding of molecular mechanisms, we can better establish the link between the early environment and adult disease. Indeed, epigenetic changes resulting from early environmental exposure are being newly discovered at a rapid pace. The goal of this review is to examine the timing of DNA methylation reprogramming and the molecular mechanisms by which this and other epigenetic marks can be modified. DNA methylation is primarily a stable repressive mark; however, its regulation is more dynamic than previously believed, and it can be actively removed at specific loci and genome-wide at several stages during development.8
The early environmental time points we focus on are the post-fertilization and germ cell differentiation stages in male and female offspring. Here we showcase examples in animals from insect to man where the environment influences the epigenome through early developmental exposures.