scholarly journals Impact of Maternal Obesity on Fetal Programming of Cardiovascular Disease

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 224-231 ◽  
Author(s):  
Victoria H. J. Roberts ◽  
Antonio E. Frias ◽  
Kevin L. Grove
Keyword(s):  
Cardiovascular Disease ◽  
Health Risks ◽  
Fetal Programming ◽  
Maternal Obesity ◽  
Later Life ◽  
Epidemiological Studies ◽  
Cardiovascular Development ◽  
Mechanistic Studies ◽  
In Utero Environment

The in utero environment is a key determinant of long-term health outcomes; poor maternal metabolic state and placental insufficiency are strongly associated with these long-term health risks. Human epidemiological studies link maternal obesity and offspring cardiovascular disease in later life, but mechanistic studies in animal models are limited. Here, we review the literature pertaining to maternal consequences of obesity during pregnancy and the subsequent impact on fetal cardiovascular development.

scholarly journals Glucocorticoids suppress β-cell development and induce hepatic metaplasia in embryonic pancreas

2003 ◽  
Vol 375 (1) ◽  
pp. 41-50 ◽  
Author(s):  
Chia-Ning SHEN ◽  
Jonathan R. SECKL ◽  
Jonathan M. W. SLACK ◽  
David TOSH
Keyword(s):  
Transcription Factor ◽  
Fetal Programming ◽  
Later Life ◽  
Dominant Negative ◽  
Β Cells ◽  
Organ Cultures ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Embryonic Pancreas ◽  
Factor C

Elevated glucocorticoids are associated with low birth weight and fetal ‘programming’ of hypertension and glucose intolerance. In the present paper, we show that treatment of fetal rats with dexamethasone during the last week of gestation reduces the insulin content of their pancreatic β-cells. We reproduce this effect of dexamethasone in vitro using organ cultures of mouse embryonic pancreas, and show that it is associated with an elevation of expression of the transcription factor C/EBPβ (CCAAT/enhancer-binding protein β) and a reduction of the transcription factor Pdx-1 (pancreatic duodenal homeobox-1). Dexamethasone also induces the appearance of hepatocyte-like cells in organ cultures of pancreas, based on the expression of liver markers, albumin, α1-antitrypsin and transthyretin. Evidence that C/EBPβ is responsible for compromising the differentiation and later function of β-cells is obtained from its effects on the β-cell-like cell line RIN-5F. Transfection with a constitutive form of C/EBPβ suppresses insulin formation, whereas introduction of a dominant-negative inhibitor of C/EBPβ has no effect. We conclude that dexamethasone inhibits insulin expression in pancreatic β-cells via a mechanism involving down-regulation of Pdx-1 and induction of C/EBPβ. This mechanism may operate in combination with other changes during fetal programming, leading to type 2 diabetes in later life.

Early Changes in Vascular Dynamics in Relation to Twin-Twin Transfusion Syndrome

Twin Research ◽  
2001 ◽  
Vol 4 (5) ◽  
pp. 371-377 ◽  
Author(s):  
Helena M. Gardiner
Keyword(s):  
Fetal Programming ◽  
Laser Photocoagulation ◽  
Pulse Wave ◽  
Twin Pair ◽  
Disease Process ◽  
Vascular Tree ◽  
Control Groups ◽  
Arterial Distensibility ◽  
Vascular Bed ◽  
Increased Risk

AbstractAclearer understanding of the early determinants of normal and abnormal vascular development is pivotal in order to identify those at increased risk of later vascular disease, and perhaps to prevent it by early intervention. Measurement of pulse wave velocity(PWV) has been used in the postnatal evaluation of the monochorionic(MC) twins. They are genetically identical and those with twin-twin transfusion syndrome(TTTS) provide an ideal natural model in whom to study the influence of differing haemodynamic stresses on the developing vascular tree. We investigated firstly whether surviving twin pairs with TTTS have altered arterial distensibility in childhood by comparing PWV in the radial arteries of surviving MC twin pairs with TTTS and in two control groups, one cohort of MC twins without TTTS and another dichorionic group (DC) Secondly, we tested a cohort of TTTS twin pair survivors treated with laser photocoagulation. The co-twin pairs in the group managed palliatively with amnioreduction showed increased PWV in the donor and reduced PWV in the recipient twins. This was neither seen in the laser-treated, nor in the control groups. Our studies suggest that a period of haemodynamic imbalance gives rise to changes in a muscular conduit artery that persist at least into infancy and it seems that by correcting the abnormal haemodynamics relatively soon after the disease process had begun, the alterations in elasticity are prevented. These studies are the first to demonstrate fetal programming of the vascular bed in humans, and prevention or reversal of this programming by an intervention in mid-gestation.

scholarly journals Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity

2013 ◽  
Vol 45 (19) ◽  
pp. 889-900 ◽  
Author(s):  
Alina Maloyan ◽  
Sribalasubashini Muralimanoharan ◽  
Steven Huffman ◽  
Laura A. Cox ◽  
Peter W. Nathanielsz ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Fetal Programming ◽  
Noncoding Rna ◽  
Animal Studies ◽  
Developmental Disorders ◽  
Maternal Obesity ◽  
Cardiac Development ◽  
Later Life ◽  
Cardiac Response ◽  
Putative Gene

Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD.

scholarly journals Can Thrifty Gene(s) or Predictive Fetal Programming for Thriftiness Lead to Obesity?

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Ulfat Baig ◽  
Prajakta Belsare ◽  
Milind Watve ◽  
Maithili Jog
Keyword(s):  
Mathematical Model ◽  
Social Factors ◽  
Fetal Programming ◽  
Later Life ◽  
Thrifty Gene ◽  
Factors Affecting ◽  
Thrifty Phenotype ◽  
Obesity Research ◽  
Thrifty Genes ◽  
Periodic Starvation

Obesity and related disorders are thought to have their roots in metabolic “thriftiness” that evolved to combat periodic starvation. The association of low birth weight with obesity in later life caused a shift in the concept from thrifty gene to thrifty phenotype or anticipatory fetal programming. The assumption of thriftiness is implicit in obesity research. We examine here, with the help of a mathematical model, the conditions for evolution of thrifty genes or fetal programming for thriftiness. The model suggests that a thrifty gene cannot exist in a stable polymorphic state in a population. The conditions for evolution of thrifty fetal programming are restricted if the correlation between intrauterine and lifetime conditions is poor. Such a correlation is not observed in natural courses of famine. If there is fetal programming for thriftiness, it could have evolved in anticipation of social factors affecting nutrition that can result in a positive correlation.

Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming

2002 ◽  
Vol 88 (5) ◽  
pp. 471-477 ◽  
Author(s):  
Linda Petrie ◽  
Susan J. Duthie ◽  
William D. Rees ◽  
Josie M. L. McConnell
Keyword(s):  
Early Pregnancy ◽  
Fetal Programming ◽  
Experimental System ◽  
Later Life ◽  
Maternal Serum ◽  
Dietary Interventions ◽  
Maternal Malnutrition ◽  
Low Protein ◽  
Underlying Mechanisms ◽  
Rats And Mice

Maternal malnutrition can lead to fetal abnormalities and increase susceptibility to disease in later life. Rat models have been developed to study the physiology and metabolism underlying this phenomenon. One particular model of 50% protein restriction during pregnancy, the low-protein diet (LPD) supplemented with methionine, has been developed to investigate the underlying mechanisms. Recent studies have shown that rats fed a LPD during only the first 4 d of pregnancy produce offspring that develop hypertension. These results suggest that the very earliest stages of embryo development are susceptible to diet-induced heritable changes. We demonstrate a marked elevation of maternal serum homocysteine (hcy) concentrations during the initial phases of pregnancy in both rats and mice fed an LPD. Fetal growth and many of the circulating amino acids are similarly perturbed in both rats and mice fed the LPD during pregnancy, indicating that the response to the LPD diet is similar in rats and mice. These findings allow us to exploit the advantages of the mouse experimental system in future analyses aimed at understanding the molecular basis of fetal programming. Our present findings are discussed with particular reference to mechanisms which may initiate fetal programming, and to the feasibility of dietary interventions aimed at reducing early pregnancy loss and pre-eclampsia in man.

scholarly journals Prenatal Air Pollution Exposure and Placental DNA Methylation Changes: Implications on Fetal Development and Future Disease Susceptibility

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3025
Author(s):  
Terisha Ghazi ◽  
Pragalathan Naidoo ◽  
Rajen N. Naidoo ◽  
Anil A. Chuturgoon
Keyword(s):  
Heavy Metals ◽  
Dna Methylation ◽  
Air Pollution ◽  
Fetal Programming ◽  
Fetal Development ◽  
Disease Susceptibility ◽  
Current Knowledge ◽  
Later Life ◽  
In Utero ◽  
Methylation Patterns

The Developmental Origins of Health and Disease (DOHaD) concept postulates that in utero exposures influence fetal programming and health in later life. Throughout pregnancy, the placenta plays a central role in fetal programming; it regulates the in utero environment and acts as a gatekeeper for nutrient and waste exchange between the mother and the fetus. Maternal exposure to air pollution, including heavy metals, can reach the placenta, where they alter DNA methylation patterns, leading to changes in placental function and fetal reprogramming. This review explores the current knowledge on placental DNA methylation changes associated with prenatal air pollution (including heavy metals) exposure and highlights its effects on fetal development and disease susceptibility. Prenatal exposure to air pollution and heavy metals was associated with altered placental DNA methylation at the global and promoter regions of genes involved in biological processes such as energy metabolism, circadian rhythm, DNA repair, inflammation, cell differentiation, and organ development. The altered placental methylation of these genes was, in some studies, associated with adverse birth outcomes such as low birth weight, small for gestational age, and decreased head circumference. Moreover, few studies indicate that DNA methylation changes in the placenta were sex-specific, and infants born with altered placental DNA methylation patterns were predisposed to developing neurobehavioral abnormalities, cancer, and atopic dermatitis. These findings highlight the importance of more effective and stricter environmental and public health policies to reduce air pollution and protect human health.

Osteoporosis in survivors of early life starvation

2013 ◽  
Vol 19 (1) ◽  
pp. 3 ◽  
Author(s):  
George M. Weisz ◽  
William R. Albury
Keyword(s):  
World War Ii ◽  
Bone Metabolism ◽  
Fetal Programming ◽  
Early Life ◽  
Health Workers ◽  
Later Life ◽  
Long Term Effects ◽  
World War ◽  
Nutritional Deprivation ◽  
Increased Risk

The objective of this study was to provide evidence for the association of early life nutritional deprivation and adult osteoporosis, in order to suggest that a history of such deprivation may be an indicator of increased risk of osteoporosis in later life. The ‘fetal programming’ of a range of metabolic and cardiovascular disorders in adults was first proposed in the 1990s and more recently extended to disorders of bone metabolism. Localised famines during World War II left populations in whom the long-term effects of maternal, fetal and infantile nutritional deprivation were studied. These studies supported the original concept of ‘fetal programming’ but did not consider bone metabolism. The present paper offers clinical data from another cohort of World War II famine survivors – those from the Holocaust. The data presented here, specifically addressing the issue of osteoporosis, report on 11 Holocaust survivors in Australia (five females, six males) who were exposed to starvation in early life. The cases show, in addition to other metabolic disorders associated with early life starvation, various levels of osteoporosis, often with premature onset. The cohort studied is too small to support firm conclusions, but the evidence suggests that the risk of adult osteoporosis in both males and females is increased by severe starvation early in life – not just in the period from gestation to infancy but also in childhood and young adulthood. It is recommended that epidemiological research on this issue be undertaken, to assist planning for the future health needs of immigrants to Australia coming from famine affected backgrounds. Pending such research, it would be prudent for primary care health workers to be alert to the prima facie association between early life starvation and adult osteoporosis, and to take this factor into account along with other indicators when assessing a patient’s risk of osteoporosis in later life.

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