The Epigenetic Mechanisms Underlying Gamete Origin of Adult-Onset Diseases

The events occurring before and soon after birth appear to impact an individual's health throughout adulthood significantly.The pioneering work of David J.P.Barker studied the nutritional status of 2414 pregnant women and their offspring during the Dutch famine between 1944 and 1945,and convincingly connected undernutrition during pregnancy to the predisposition of offspring to many adult-onset diseases,including cardiovascular disease,aberrant glucose metabolism,hypertension,central obesity,and dyslipidemia.This not only attracted global attention but also con-tributed to the genesis of the term"developmental origins of health and disease"(DOHaD),which emphasizes the contribution of prenatal and perinatal exposure to adverse environments to the etiology of diseases in later childhood and adult life[1].A large number of subsequent clinical epidemiology and animal studies proved that both fetal exposure and infant growth patterns can sig-nificantly affect the occurrence of adult-onset diseases.Given that the phenotypic transmission is often limited to one generation and the phenotypic distribution does not follow Mendel's laws,the underlying mechanism(s)has/have been hypothesized to be epige-netic rather than genetic.