There has been a recent explosion of interest in the potential role of epigenetics as a mediator of the long-term effects of an adverse intrauterine environment. Offspring from the Dutch
Famine studied in the seventh decade of life showed increased methylation in seven loci, including igf2 and inisigf (a fusion transcript between the insulin promoter and the igf2 gene that arises from igf2/H19locus in early development), in those exposed to famine preconception, whereas exposure in late gestation was associated with increased methylation in only one locus (gnasas).Epigenetic differences in metastable epialleles also have been reported in 7-year-old offspring of women in the Gambia who conceived during the rainy season (a season of famine) compared with the harvest season.Interestingly, a study of epigenetic modifications in the igf2/H19 locus in babies born small-for-gestational-age did notfind methylation differences,indicating once again that fetal developmental adaptations in response to maternal nutrition are not causally related to altered fetal growth.Further, the relationship between maternal nutritional status and the metabolic regulation of the offspring may extend beyond the next generation.