Conclusions

Strong evidence in both human and in animal studies supports the hypothesis that hypertension can be programmed in utero. Future studies should encompass the following (1) Prehypertensive animals should be studied to differentiate between the primary initiating programming events and events secondary to the consequent development of hypertension. (2) Best practice methods should be employed to determine arterial blood pressure single time-point measures are open to misinterpretation...

References

Altered retinal function and structure after chronic placental insufficiency. Invest Ophthalmol Vis Sei 2002 43(3) 805-812. 2. Zubrick SR, Kurinczuk JJ, McDermott BM et al. Fetal growth and subsequent mental health problems in children aged 4 to 13 years. Dev Med Child Neurol 2000 42(l) 14-20. 3. Spinillo A, Stronati M, Ometto A et al. Infant neurodevelopmental outcome in pregnancies complicated by gestational hypertension and intra-uterine growth retardation....

Nephron Glomerular Number

The kidney has been implicated in the programming of adult disease predominandy through studies in which a low reduced nephron number resulting from maternal intervention is associated with elevated blood pressure in the adult offspring. Much interest has focused on the so called Brenner hypothesis which states that a reduction in nephron endowment at birth contributes to the development of hypertension.11 However, is it really that simple The normal range of glomeruli in a human kidney is...

Is Low Birth Weight a Risk for Kidney Disease

Much of the evidence for programming of adult disease comes from human epidemiological studies and animal models where the offspring is of low birth weight due to maternal undernutrition or placental insufficiency.3'4 Infants born of low birth weight, that is small for gestational age (SGA) are at increased risk of developing adult diseases particularly hypertension and noninsulin dependent diabetes mellitus (NIDDM). A link between low birth weight and renal disease is not as firmly established...

Children and Adolescents Neurodevelopmental Milestones

The literature regarding neuromotor outcomes in school-age children born IUGR is sparse and somewhat variable, both methodologically and in outcomes. This is partly because no two studies appear to have used the same assessment instrument, and the findings have been inconsistent. They range from little or no increase in the likelihood of suboptimal motor performance to significant decrements in a wide range of fine and gross motor skills. Again, none have included neurophysiological assessments...

Maternal Diet Altering Fetal Phenotype

Given the impact that diet can have on DNA methylation in an adult individual, several studies have now been undertaken to see if these effects occur during embryonic development. Rees et al demonstrated that a maternal protein-deficient diet (supplemented with threonine) led to global hypermethylation of DNA in the livers of fetal rats. The authors propose that the hypermethylation seen in the offspring is a result of threonine metabolism competing for enzymes involved in methionine...

Is It Just Nephron Number Thats Important

Arguments against the Brenner hypothesis primarily come from human and animal experiences where removal of a kidney from an adult, thereby halving the nephron number, does not generally result in hypertension. Long term follow up studies of patients who have had a kidney removed due to a tumour or donated a kidney for transplantation have not shown an increased incidence of hypertension.25 Other studies in the rat where the glucocorticoid treatment occurred earlier in gestation also show that...

Epigenetic Lability at Genomically Imprinted Genes

Genomic imprinting is an epigenetic phenomenon by which certain mammalian genes are expressed preferentially from either the paternally-inherited or maternally-inherited allele. Monoallelic expression of imprinted genes is regulated by allele-specific methylation of specific CpGs.14 Most imprinted genes are found in clusters, and these imprinted domains are regulated in coordinate fashion via long range mechanisms including antisense RNA interference and methylation-sensitive boundary...

Kidney Development

Metanephros

Renal development in mammals involves the development of three sets of excretory organs, the pronephros, mesonephros (transitory organs) and the metanephros (Fig. 1). The meta-nephros (permanent kidney) develops from two embryonic precursor cell populations, the Figure 1. Development of the permanent mammalian kidney. Schematic diagram illustrating the development of the mammalian excretory system. The pronephros and mesonephros are transitory and degenerate. The metanephros forms when the...

The Couch Potato Syndrome

We have recendy reported experimental evidence suggesting that maternal undernutrition can induce sedentary behaviour, hyperphagia and concomitant obesity in offspring independent of postnatal dietary influences. We had previously shown that maternal undernutrition throughout pregnancy in the rat results in hypertension, hyperinsulinemia and hyperleptinemia in the offspring when they reach adulthood.6 Obesity was not present until after puberty and was associated with hyperphagia. In the course...

Postnatal Nutrition

We can distinguish two conceptually different types of interactions between prenatal influences and postnatal nutrition in the pathogenesis of metabolic disorders and obesity. Diet-induced obesity during postnatal life can amplify pathogenic mechanisms established by adverse prenatal influences. Alternatively, changes caused by prenatal influences can facilitate a disease process that is induced by postnatal environmental factors such as nutrition. An example is the development of obesity and...

Maternal Stress and Motor Development in the Offspring

Apart from sub-optimal nutrition in utero, another source for altered prenatal programming of motor development is maternal stress. Maternal stress during pregnancy has also been shown to impair neuromotor development in rats and non-human primates, although the number of studies is relatively small. The gestational timing at which maternal stress occurs appears to determine the type of adverse affect on neuromotor development and outcomes.102 In rats, acquisition of a range of precocious...

H

Heart 1-3, 5, 8, 14, 20, 33, 88, 103, 113, 114, 125, 127, 158, 159, 187, 189, 191, 192, 200, 220 Hertfordshire 9-12, 14, 15, 19 High altitude 220-223 High blood pressure 90, 103, 104, 109, 113, 131, 132, 138, 159,219 Histone modification 71 Hypertension 3, 8-10, 19, 20, 31, 70, 74-76, 87, 88, 90, 91, 94, 103-114, 121, 123, 126,130-132, 138-140,146, 147, 150, 151, 153, 179-181, 198, 199, 223 Hypertensive pregnancy 107, 108 Hypobaria 220 Hypothalamo-pituitary-adrenal (HPA) axis 2, 3, 5, 16, 146,...

The History of the Neurodevelopmental Hypothesis

The neurodevelopmental hypothesis proposes that adverse environmental events during fetal life impairs and subsequendy alter neural development, leading to mental illness in adulthood.10'14 Like all good theories, it has a long history. As early as 1891, the founding father of adolescent psychiatry, Scottish psychiatrist Thomas Storer Clouston, proposed that there was a developmental component to adolescent or developmental insanity. He considered it a disorder of cortical development the last...

Summary and Conclusions

Numerous epidemiological studies have shown that perturbations in early life can have persistence consequences for health in later life. Both prospective clinical studies and experimental research have clearly shown that the propensity to develop abnormalities of cardiovascular, endocrine and metabolic homeostasis in adulthood is increased when fetal development has been adversely affected. The pathogenesis is not based on genetic defects but on altered genetic expression as a consequence of an...

Prenatal Programming of Human Motor Function

Henderson-Smart and Jeffrey S. Robinson Abstract In a world in which athletic skill is often valued more highly than intellectual prowess, we know surprisingly litde about the development of the human motor system. Even less is known about how an adverse intrauterine event or environment might program motor learning, memory and function throughout the lifespan. We are only beginning to investigate how events during development of the brain and central nervous system...

Springer Science Business Media Landes Bioscience Eurekahcom

Springer Science Business Media Eurekah.com Landes Bioscience Copyright '2006 Eurekah.com and Springer Science Business Media All rights reserved. No part of this book may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without permission in writing from the publisher, with the exception of any material supplied specifically for the purpose of being entered and executed on a...

Programming of the Adipoinsular Axis and Altered Adipogenesis

It is important to note that very few animal studies have addressed interactions between pre and postnatal nutrition. However, other studies that have investigated diet-induced obesity point to a link between peripheral leptin resistance and insulin resistance in the development of obesity. The physiological role of hyperleptinemia associated with caloric excess has been proposed to relate to the protection of nonadipocytes from lipid oversupply that would lead to steatosis and lipotoxicity.68...

Nicola Vickaryous and Emma Whitelaw Abstract

The unraveling of the human genome is revealing the intertwined nature of epigenetic phenomena and the genetic code. Epigenetic modifications can alter patterns of gene expression, independent of DNA sequence mutation. Instead, epigenetic marks modify the existing DNA sequence. These modifications include cytosine methylation in the promoter region of genes, a phenomena associated with transcriptional silencing, and recruitment of chromatin remodeling complexes. Epigenetic marks are established...

Developmental Origins of Cardiovascular Disease Type 2 Diabetes and Obesity in Humans

Fetal Origins Adult Disease

Fetal growth restriction and low weight gain in infancy are associated with an increased risk of adult cardiovascular disease, type 2 diabetes and the Metabolic Syndrome. The fetal origins of adult disease hypothesis proposes that these associations reflect permanent changes in metabolism, body composition and tissue structure caused by undernutrition during critical periods of early development. An alternative hypothesis is that both small size at birth and later disease have a common genetic...

Epigenetic Lability at Transposable Elements

Except for a brief period of global demethylation in the early mammalian embryo, transposable elements in the genome are generally silenced by hypermethylation.15 However, these parasitic elements comprise over 45 of the mammalian genome, and their aberrant transcriptional activity can interfere with the expression of neighboring genes.32 Dysregulation of even a small fraction of human transposable elements could therefore cause substantial genomic instability.15'29 Notably, transposable...