Prenatal Undernutrition, Glucocorticoids And The Programming Of Adult Hypertension

Abstract

1. A range of epidemiological studies has shown that poor intra-uterine growth is associated with an increased prevalence of cardiovascular disease, non-insulin-dependent diabetes mellitus and the Metabolic syndrome in adult life. 2. Because these associations are independent of adult lifestyle or current size, it has been postulated that a reduced intra- uterine nutrient supply perturbs fetal growth and, concomitantly, alters or programmes the structure and function of developing systems. 3. A reduced fetal nutrient supply may be a consequence of poor placental function or inadequate maternal nutrient intake. 4. It has been proposed that one outcome of either a suboptimal placental or maternal nutrient supply is exposure of the fetus to excess glucocorticoids, which act to restrict fetal growth and to programme permanent changes in the cardiovascular, endocrine and metabolic systems. 5. While a range of studies in the rat has investigated the impact of maternal undernutrition on arterial blood pressure in the offspring, there have been relatively few studies in species, such as the sheep, in which the responses of the cardiovascular and neuroendocrine systems to intra-uterine undernutrition can be measured before birth. 6. The present review summarizes recent evidence that poor placental function or inadequate maternal nutrition each results in an increased exposure of fetal sheep tissues to glucocorticoids and, in specific, changes in the regulation of fetal arterial blood pressure. 7. These studies are important in determining how the timing, type and duration of fetal nutrient restriction are each important in determining the nature of the fetal neuroendocrine and cardiovascular adaptive responses and their pathophysiological sequelae in later life.

Dietary Recommendations for Children and Adolescents: A Guide for Practitioners

“…Animal models support the programming hypothesis, but there are as yet few human experimental data. [85][86][87] Lower birth weight, because of presumed intrauterine malnutrition and association with rapid postnatal rapid weight gain, is associated with central adiposity, the metabolic syndrome, diabetes mellitus, and cardiovascular disease outcomes in adulthood. 88 Infants large for gestational age, probably through consequences of maternal insulin resistance and glucose intolerance, are also at higher risk of future obesity.…”

Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring

“…[7][8][9][10] In animal models of hypertension in which female rats are normotensive relative to their hypertensive male counterparts, ovariectomy induces hypertension. 11-14 Therefore, it seems that, while the ovaries are functional, women have a lower risk of cardiovascular disease than men, an observation supported by experimental studies.Alterations in the fetal environment during a critical period of fetal development result in fetal adaptive changes that lead to long-term consequences, such as increased risk for development of hypertension and cardiovascular disease later in life, [15][16][17][18][19] an observation supported by numerous animal models. 19 -22 Sex differences are reported in different animal models of fetal programming; male offspring develop vascular dysfunction and hypertension, whereas female offspring seem to be protected.…”

“…Alterations in the fetal environment during a critical period of fetal development result in fetal adaptive changes that lead to long-term consequences, such as increased risk for development of hypertension and cardiovascular disease later in life, [15][16][17][18][19] an observation supported by numerous animal models. 19 -22 Sex differences are reported in different animal models of fetal programming; male offspring develop vascular dysfunction and hypertension, whereas female offspring seem to be protected.…”

Early foetal programming of hepatic gluconeogenesis: glucocorticoids strike back

“…Numerous laboratories have, however, provided compelling evidence that foetal exposure to inappropriate amounts of glucocorticoids has profound effects on foetal growth, placental function, and foetal and post-natal brain development, and can result in persistent hyperglycaemia throughout life [9][10][11]. Suboptimal maternal nutrition [12] and maternal stress [13,14] are also thought to expose the foetus to excess glucocorticoids. Regardless of the source, elevated glucocorticoid levels during pregnancy predispose to in utero growth retardation and low birthweight [15,16].…”