Metabolic disorders: Fathers' nutritional legacy

Abstract

A female can develop a diabetes-like disease due to a high fat content in her father's diet before she was conceived. Epigenetic modifications of the father's sperm DNA might underlie this peculiar observation. See Letter p.963

Figure 1. Environmental effects across generations

Whereas most environmental factors cannot alter an animal's DNA sequence, many promote epigenetic alterations that influence somatic cells and so the disease status of the individual exposed (F₀ generation). In pregnant females, environmental exposure could also cause epigenetic modifications in the next two generations (F₁ and F₂) through the fetus and its germ line. The effect of such multigenerational exposure in subsequent generations (F₃ and beyond) would be considered a transgenerational phenotype. By contrast, multigenerational exposure in males is limited to the F₀ and F₁ generations. Ng and colleagues' observations fit well into a multigenerational exposure. However, they did not explore whether the high-fat diet of their male rats also causes a transgenerational phenotype in the F₂ generation.