Developmental Origins of Health and Disease (DOHaD)

Takeo Kubota, Kubota, Takeo

The developmental origins of health and disease (DOHaD) refers to the concept that environmental stress during pregnancy alters the programmed fetal development and subsequently causes disorders, such as cardiovascular and metabolic diseases, in adulthood. Epigenetics is a gene regulation mechanism that does not depend on DNA sequence but on chemical modifications of DNA. Several lines of evidence suggest that environmental stress in the fetal period alters the epigenetic state of genes, leading to permanent gene dysregulation, which may be associated with disorders that emerge after birth. Such stresses include malnutrition, which may be associated with type 2 diabetes, and mental stress, which may be associated with neurodevelopmental disorders. It has also been demonstrated that environmental stress-induced epigenetic alterations can be transmitted to the next generation via disease phenotypes. However, since epigenetic modification is an internal system based on attachment and detachment of chemical residues on a DNA sequence, it is reversible and potentially treatable. In fact, recent studies demonstrated that some drugs and early interventions are effective at preventing epigenetic disorders. Therefore, preventive and preemptive medicine is possible for disorders caused by alterations in programming during fetal and early periods.