Early-life programming of livestock metabolism by glucocorticoids

Adverse environmental conditions during early life are known to determine adult metabolic phenotype in laboratory species and human populations. However, less is known about developmental programming of adult metabolic phenotype in livestock, given their size and longevity compared to laboratory animals. As maternal and/or fetal glucocorticoid (GC) concentrations rise in stressful conditions during pregnancy, GCs may act as a common mechanism linking early-life environmental conditions to the subsequent metabolic phenotype. This review examines prenatal and longer-term postnatal programming of metabolism by early-life GC overexposure in livestock species with a particular emphasis on sheep. It examines the effects of both cortisol, the natural glucocorticoid and more potent synthetic GCs used clinically to treat threatened pre-term delivery and other conditions during pregnancy. It considers the effects of early- life GC overexposure on the metabolism of specific feto-placental and adult tissues in relation to changes in the growth trajectory, other metabolic hormones and in the functioning of the hypothalamic-pituitary-adrenal axis itself. It highlights the role of GCs as maturational and environmental signals in programming development of a metabolic phenotype fit for survival at birth and future homeostatic challenges. However, the ensuing metabolic phenotype induced by early GC overexposure may become inappropriate for the prevailing postnatal conditions and lead to metabolic dysfunction as functional reserves decline with age. Further studies are needed in livestock to establish whether the metabolic outcomes of early-life GC overexposure are sex-linked, more pronounced in old age and inherited transgenerationally in these species.