The fetus and neonate pass through critical periods which permanently determine cardiovascular and endocrine control. Such programming can occur covertly in fetal life, and may ultimately have deleterious consequences for the adult.
Animal models demonstrate that maternal dietary imbalance produces offspring with elevated blood pressure and perturbed HPA axis responses. However, the late gestation fetus is not hypertensive, and models such as carunclectomy or placental embolisation do not uniformly produce hypertensive late gestation fetuses/ neonates. But links between postnatal growth rate and blood pressure illustrate how programming can confer susceptibility to hypertension. Studies of isolated small resistance arteries give clues to the mechanisms by which hypertension arises.
Such programming can occur early in gestation, since a low protein diet during the pre-implantation period in the rat reduces birthweight and elevates blood pressure in the offspring. The prenatal growth trajectory then sets the scene for the interactions between the growing newborn and its environment. New epidemiological data reveals how the pattern of early childhood growth is linked to the risk of cardiovascular disease.
The HPA axis is a prime suspect in fetal programming. Effects on the fetal HPA axis are exerted at several levels, including suppression of fetal pituitary and adrenal responses. However, reduced pituitary glucocorticoid receptor expression indicates that postnatal responses will be exaggerated, as found in humans and animals. Tissue-specific increases in glucocorticoid receptor expression, and reductions in 11β-HSD-2 activity may explain effects on growth and development of key organs such as the kidney, and also hypertension and insulin resistance. Postnatal environmental factors including diet and other stressors may hold the key to which susceptible individuals go on to develop overt disease, and how it may be prevented.
03 - 04 Dec 2001
Society for Endocrinology