Fetal programming of CVD and renal disease: animal models and mechanistic considerations

Abstract

The developmental origins of health and disease hypothesis postulates that exposure to a less than optimal maternal environment during fetal development programmes physiological function, and determines risk of disease in adult life. Much evidence of such programming comes from retrospective epidemiological cohorts, which demonstrate associations between birth anthropometry and non-communicable diseases of adulthood. The assertion that variation in maternal nutrition drives these associations is supported by studies using animal models, which demonstrate that maternal under-or over-nutrition during pregnancy can programme offspring development. Typically, the offspring of animals that are undernourished in pregnancy exhibit a relatively narrow range of physiological phenotypes that includes higher blood pressure, glucose intolerance, renal insufficiency and increased adiposity. The observation that common phenotypes arise from very diverse maternal nutritional insults has led to the proposal that programming is driven by a small number of mechanistic processes. The remodelling of tissues during development as a consequence of maternal nutritional status being signalled by endocrine imbalance or key nutrients limiting processes in the fetus may lead to organs having irreversibly altered structures that may limit their function with ageing. It has been proposed that the maternal diet may impact upon epigenetic marks that determine gene expression in fetal tissues, and this may be an important mechanism connecting maternal nutrient intakes to long-term programming of offspring phenotype. The objective for this review is to provide an overview of the mechanistic basis of fetal programming, demonstrating the critical role of animal models as tools for the investigation of programming phenomena.

Glucocorticoids and foetal heart maturation; implications for prematurity and foetal programming

“…Maternal nutritional restriction, which prematurely activates the foetal HPA axis (Cottrell et al 2012), also increases foetal glucocorticoid levels and 'programmes' greater risk of cardiovascular disease once adult (Langley-Evans et al 1998, Roseboom et al 2001, as does maternal stress, probably through increased maternal glucocorticoid levels , Bingham et al 2013). Glucocorticoid and/or nutritional programming of adult disease has been extensively reviewed (for recent reviews see , Langley-Evans (2013) and Reynolds (2013)). In addition, the reader is referred to a comprehensive recent review of the acute effects of betamethasone and dexamethasone on human foetal behaviour (movement/breathing) and haemodynamics (heart rate, Doppler velocity measurements of blood flow in the umbilical artery) (Mulder et al 2009).…”

Epigenetics and developmental programming of welfare and production traits in farm animals

“…Since then, a plethora of studies has been conducted both in humans and in a variety of animal model species, including farm animals, that support these initial observations, and these have been the subject of extensive review and meta-analysis in recent years (e.g. McMillen and Robinson 2005;Gluckman et al 2008;Fowler et al 2012;Thayer et al 2012;Langley-Evans 2013;Steegers-Theunissen et al 2013).…”

Do little embryos make big decisions? How maternal dietary protein restriction can permanently change an embryo’s potential, affecting adult health

“…There are some excellent reviews embracing rodent and larger animal models and considering the programming effects of both maternal under-and overnutrition (Ford and Long 2011;Langley-Evans 2013, 2015Williams et al 2014;Zambrano et al 2014). A major theme to emerge from across these studies is that nutrition during pregnancy is indeed an environmental factor that can activate physiological interactions between mother and conceptus, mediated through diverse mechanisms including hormonal signalling that may cause epigenetic changes in regulatory genes within target tissues.…”