An Analysis of Transgenerational Epigenetic Inheritance and Potential Implications for Obesity in Humans

Abstract

Transgenerational epigenetic inheritance is characterized by the persistence of epigenetic changes over multiple generations. This has been documented in certain plants, C. elegans, and Drosophila, but a number of researchers now claim that changes to the diet can induce epigenetic changes that persist transgenerationally in mice as well. However, given that in mammalian development, epigenetic modifications are reset at the start of each generation, it is essential to reconcile transgenerational epigenetic inheritance with epigenetic reprogramming. If it can indeed occur in mammals, it would greatly influence our understandings of gene-environment interactions, heritable diseases, and evolution. Thus, this thesis aims to analyze these claims of transgenerational epigenetic inheritance in mammals, focusing on the literature and implications for obesity. A complex disease known to arise from both genetic and environmental factors, obesity may now be shaped by transgenerational epigenetic inheritance as well. By analyzing the primary literature that focuses on metabolic effects, this thesis examines this issue from a theoretical perspective, by considering potential mechanisms and confounding factors, and from an experimental perspective by evaluating epidemiological studies and animal studies. To date, trends from parents or grandparents to their offspring have been detected in numerous contexts, where the most compelling evidence is associated with male-line transmission. As a mechanism by which such transmission might occur is elusive, however, this thesis offers one version of the “perfect” experiment to prove or disprove transgenerational epigenetic inheritance. If it can occur, epigenetic changes caused by our diets today may influence our descendants’ metabolism in future generations.