The understanding of how gene and the environment interact in controlling disease can now be expanded to include epigenetic reprogramming, which is a key determinant of origins of human disease and development. Epigenetics is defined as heritable changes in gene expression that do not alter DNA sequence but are mitotically and trans-generationally inheritable. Epigenetic reprogramming is the process by which an organism’s genotype interacts with the environment to produce its phenotype. This provides a framework for explaining individual variations and the uniqueness of cells, tissues, or organs despite identical genetic information. The main epigenetic mediators are DNA methylation, histone modification, and non-coding RNAs that regulate crucial cellular functions, and occur during human gametogenesis and early embryonic development along the germ line. Deficiencies in remodeling this epigenome can cause severe developmental defects, infertility, and long-term health issues in offspring. Parental diets, unhealthy parental habits and environmental factors such as exercise, social interaction and climate change may disturb the epigenetic reprogramming processes leading to an aberrant epigenome in the offspring. Here, we review the effects of parental environmental exposures on the epigenetics of gametes and the early embryo, and how those changes influence transgenerational inheritance in humans and rats.
