Epigenetic regulation of the fetal circadian clock

Abstract Nutritional disturbances during in utero life can disrupt fetal development and thereby “program’ the subsequent metabolic phenotype in adulthood. Maternal nutritional status is thus a key determinant of the intrauterine environment quality. Offspring born to nutritionally compromised pregnancies, such as those complicated by maternal obesity, undernutrition, or micronutrient deficiencies, often experience developmental aberrations and associated metabolic pathologies in adulthood. A growing body of evidence indicates that these nutritionally programmed metabolic complications are mediated via fetal epigenetic changes, including shifts in DNA methylation, histone structure and non-coding RNA activity. Moreover, because metabolic processes are intimately linked to circadian biology, clock gene networks have emerged as potential mediators of the programmed metabolic phenotype. In this chapter, we explore the evidence supporting a role for nutritional signals in utero affecting fetal clock and clock-controlled systems via permanent effects on the fetal epigenome, thereby leading to metabolic health complications in postnatal life.