Developmental Origins Of Adult Disease Research Articles

The developmental origin of adult diseases: The effect of intrauterine environment on the vascular proteomic profile in later life

We have previously shown that vascular function in adult mice offspring heterozygous for a non-functioning NOS3 allele depends on whether they developed in a normal mother or one lacking a functional NOS3, independent of the offspring's genomic profile. Our objective was to use proteomics to identify and characterize protein expressions responsible for the altered vascular responses seen in later life in our model of vascular programming.

Integrating the Ideas of Life Course across Cellular, Individual, and Population Levels in Cancer Causation

Cells, individuals, and societies are complex systems in which the integrity of structure and function is protected through tight regulation and control. For each level of organization, health represents the ability to maintain integrity in response to the wider environment. Critical stages during growth and development act as checkpoints, where choice is exercised, and help determine future direction. Important among factors influencing the checkpoints include the availability of nutrients or foods within the immediate environment. At the cellular and whole-body levels, this information can be communicated to future generations. Recent work on the developmental origins of adult disease indicate specific factors that set limits on structure and function and potentially limit the capacity of the cell and individual to respond to environmental stressors that represent potential risk factors for neoplastic change. Epigenetic mechanisms modulate structure and function at the cellular and tissue levels, reflecting the potential for the growth and development of individuals, and reflect the food and nutrients available to the body as a whole and within the wider society. Understanding the nature and the interaction of the critical factors that determine and regulate variable stable and unstable gene expression will be increasingly important in characterizing abnormal cellular function and risk of disease for individuals and populations. This will require the ability to synthesize large data sets within and between different levels of organization to develop and refine a deeper understanding of how the systems are effectively integrated and regulated within and across generations and where this fails in the genesis of cancer.

The developmental origins of adult disease.

Epidemiological and clinical observations have led to the hypothesis that the risk of developing some chronic diseases in adulthood is influenced not only by genetic and adult lifestyle factors, but also by environmental factors acting in early life. These factors act through the processes of developmental plasticity and possibly epigenetic modification, and can be distinguished from developmental disruption. The concept of predictive adaptation has been developed to explain the relationship between early life events and the risk of later disease. At its base, the model suggests that a mismatch between fetal expectation of its postnatal environment and actual postnatal environment contribute to later adult disease risk. This mismatch is exacerbated, in part, by the phenomenon of "maternal constraint" on fetal growth, which implicitly provides an upper limit of postnatal nutritional environment that humans have adapted for and is now frequently exceeded. These experimental, clinical and conceptual considerations have important implications for prevention and intervention in the current epidemic of childhood obesity and adult metabolic and cardiovascular disorders.

Molecular, cellular and endocrine signalling in the perinatal cardiovascular system: interplay and developmental programming

Molecular, cellular and endocrine signalling in the perinatal cardiovascular system: interplay and developmental programming

Developmental origins of adult disease: Barker's or Dörner's hypothesis?

Developmental origins of adult disease: Barker's or Dörner's hypothesis?

The Developmental Origins of Adult Disease

Low birthweight is now known to be associated with increased rates of coronary heart disease and the related disorders stroke, hypertension and non-insulin dependent diabetes. These associations have been extensively replicated in studies in different countries and are not the result of confounding variables. They extend across the normal range of birthweight and depend on lower birthweights in relation to the duration of gestation rather than the effects of premature birth. The associations are thought to be consequences of developmental plasticity, the phenomenon by which one genotype can give rise to a range of different physiological or morphological states in response to different environmental conditions during development. Recent observations have shown that impaired growth in infancy and rapid childhood weight gain exacerbate the effects of impaired prenatal growth. A new vision of optimal early human development is emerging which takes account of both short and long-term outcomes.

The fetal, neonatal, and infant environments—the long-term consequences for disease risk

The developmental origins of health and disease can be understood by reference to the fundamentals of developmental plasticity. It is essential to distinguish between those environmental effects acting during development that are disruptive from those that have adaptive value. The latter are likely to underpin programming and the developmental origins of adult disease. It is suggested that greater disease risk is created by a mismatch between the environment predicted during the plastic phase of development and the actual environment experienced in the postplastic phase. This plastic phase extends from conception to after birth at least for some systems. It is not necessary to invoke a particular mechanism in the neonatal or infant period. There is increasing evidence that prematurity can be associated with long-term consequences, and this is to be anticipated from conceptual considerations. Different preventative strategies may be relevant in different populations.

Sex and preterm brain development

The brains of preterm infants grow differently than do the brains of term infants. These differences in brain volumes and structures can be detected at term and subsequently through childhood by magnetic resonance imaging (MRI). The different brain volumes in preterms relative to term also correlate with differences in regional brain functions as assessed by functional MRI. Reiss et al now demonstrate in The Journal that decreased white matter volumes were measured in preterm males relative to term males at 8 years of age. However, differences between preterm females and term females at 8 years were not evident. In contrast, grey matter volumes correlated with cognitive function in girls but not boys. These observations are important to learning how the preterm brain develops during childhood. Sex is a variable in a number of animal models of developmental origins of adult diseases. Corticosteroid treatments may alter development in one sex but not the other, for example. This paper by Reiss et al points out that sex needs to be considered for human studies of outcomes after events that may alter subsequent development. In this case, that event is preterm delivery.Page 242 The brains of preterm infants grow differently than do the brains of term infants. These differences in brain volumes and structures can be detected at term and subsequently through childhood by magnetic resonance imaging (MRI). The different brain volumes in preterms relative to term also correlate with differences in regional brain functions as assessed by functional MRI. Reiss et al now demonstrate in The Journal that decreased white matter volumes were measured in preterm males relative to term males at 8 years of age. However, differences between preterm females and term females at 8 years were not evident. In contrast, grey matter volumes correlated with cognitive function in girls but not boys. These observations are important to learning how the preterm brain develops during childhood. Sex is a variable in a number of animal models of developmental origins of adult diseases. Corticosteroid treatments may alter development in one sex but not the other, for example. This paper by Reiss et al points out that sex needs to be considered for human studies of outcomes after events that may alter subsequent development. In this case, that event is preterm delivery. Page 242

Maternal nutrient restriction reduces concentrations of amino acids and polyamines in ovine maternal and fetal plasma and fetal fluids.

Amino acids and polyamines are essential for placental and fetal growth, but little is known about their availability in the conceptus in response to maternal undernutrition. We hypothesized that maternal nutrient restriction reduces concentrations of amino acids and polyamines in the ovine conceptus. This hypothesis was tested in nutrient-restricted ewes between Days 28 and 78 (experiment 1) and between Days 28 and 135 (experiment 2) of gestation. In both experiments, ewes were assigned randomly on Day 28 of gestation to a control group fed 100% of National Research Council (NRC) nutrient requirements and to an nutrient-restricted group fed 50% of NRC requirements. Every 7 days beginning on Day 28 of gestation, ewes were weighed and rations adjusted for changes in body weight. On Day 78 of gestation, blood samples were obtained from the uterine artery and umbilical vein for analysis. In experiment 2, nutrient-restricted ewes on Day 78 of gestation either continued to be fed 50% of NRC requirements or were realimented to 100% of NRC requirements until Day 135. Fetal weight was reduced in nutrient-restricted ewes at both Day 78 (32%) and Day 135 (15%) compared with controls. Nutritional restriction markedly reduced (P < 0.05) concentrations of total alpha-amino acids (particularly serine, arginine-family amino acids, and branched-chain amino acids) and polyamines in maternal and fetal plasma and in fetal allantoic and amniotic fluids at both mid and late gestation. Realimentation of nutrient-restricted ewes increased (P < 0.05) concentrations of total alpha-amino acids and polyamines in all the measured compartments and prevented intrauterine growth retardation. These novel findings demonstrate that 50% global nutrient restriction decreases concentrations of amino acids and polyamines in the ovine conceptus that could adversely impact key fetal functions. The results have important implications for understanding the mechanisms responsible for both intrauterine growth retardation and developmental origins of adult disease.