Significance: Epigenetic modifications are key processes in understanding normal human development and are largely responsible for the myriad cell and tissue types that originate from a single-celled fertilized ovum. The three most common processes involved in bringing about epigenetic changes are DNA methylation, histone modification, and miRNA effects. There are critical periods in the development of the zygote, the embryo, and the fetus where in the organism is most susceptible to epigenetic influences because of normal demethylation and de novo methylation processes that occur in the womb.
Recent advances: A number of epigenetic modifications of normal growth patterns have been recognized, leading to altered development and disease states in the mammalian fetus and infant. 'Fetal programming' due to these epigenetic changes has been implicated in pathogenesis of adult-onset disease such as hypertension, diabetes, and cardiovascular disease. There may also be transgenerational effects of such epigenetic modifications.
Critical issues: The impact of environmental agents and endogenous factors such as stress at critical periods of infant development has immediate, life-long and even multi-generational effects. Both the timing and the degree of insult may be important. Understanding these influences may help prevent onset of disease and promote normal growth.
Future directions: Use of one-carbon metabolism modifying agents such as folic acid during critical periods of epigenetic modulation may have significant clinical impact. Their use as therapeutic agents in targeted epigenetic modulation of genes may be the new frontier for clinical therapeutics.