title: 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.
authors: School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK. Simon.Langley-Evans@Nottingham.ac.uk
authors: Simon C
authors: SC
authors: Langley-Evans
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000209:etiology*; D004195:Disease Models, Animal; D005260:Female; D047109:Fetal Development / Q000502:physiology*; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena / Q000502:physiology*; D011247:Pregnancy