1,720,997 research outputs found
External influences on the fetus and their long-term consequences
No full textThe observation that low birth weight is associated with cardiovascular disease and its risk factors has formed the basis for the ‘developmental origins' hypothesis. This hypothesis suggests that the operation of adverse influences during intrauterine life leads to permanent alterations in structure and physiology of the adult phenotype which predispose to a range of common adult diseases. The process is known as developmental plasticity or programming and is strongly supported by studies in experimental animals. Recent evidence suggests that the same processes may affect the development of the immune system and play a part in the pathogenesis of autoimmune disease. Animal studies show that the intrauterine environment has powerful and long-lasting effects on many aspects of immune function. The corresponding human evidence, though preliminary, suggests that birth weight or other markers of the early environment are associated with a range of autoimmune diseases
Symposium. Programming of the stress response: a fundamental mechanism underlying the long-term effects of the fetal environment?
No full textThere is a large body of evidence which suggests that an adverse fetal environment results in a heightened biobehavioural response to stress, with increased activity of the classical mediators of the stress response, including the hypothalamic-pituitary adrenal axis and autonomic nervous system. Although this has been amply demonstrated in animal experiments, several recent studies suggest that the same processes operate in human populations and may have important consequences for health. The evidence suggests that an adverse early environment or markers of an adverse environment such as low birth weight are linked with long-term alterations in these neuroendocrine systems. However, these studies also demonstrate that there is a considerable degree of heterogeneity in the responses observed which appear to depend on a variety of factors such as the nature or timing of the adverse exposure as well as the gender of the offspring. The mediators of these classical neuroendocrine responses such as cortisol and catecholamines are biologically potent and may directly influence disease susceptibility by means of their effects on metabolism and the vasculature. However, lifelong changes in the set point of these neuroendocrine systems in response to the early environment may also direct the course of development during fetal life, infancy and childhood towards the generation of a phenotype adapted for the adult environment predicted by the clues available during fetal life. This has biological advantages if the actual adult environment turns out to be appropriate for the phenotype. However, ill health may occur if the phenotype is not well matched to the actual environment encountered in adult life
Birthweight and adult disease and the controversies
No full textA large number of studies show that low birth weight is associated with cardiovascular disease and its risk factors including raised blood pressure, glucose intolerance and the metabolic syndrome. These findings have formed the basis for the ‘fetal origins hypothesis’. This suggests that the operation of adverse influences during intrauterine life leads to permanent alterations in fetal structure and physiology which predispose to adult disease. The process is known as developmental plasticity or programming and is strongly supported by studies in experimental animals. Ongoing research is providing important insights in to the underlying mechanisms. It is likely that adverse environmental factors during pregnancy are important, and that these include suboptimal nutrition of the mother. The long-term programming effects may be transduced by alterations in the set-point of key hormonal axes, especially the hypothalamic-pituitary-adrenal axis, and recent evidence suggests that epigenetic modification of gene expression may be a key factor. Importantly, this has the potential to produce transgenerational effects.The hypothesis has not remained unchallenged and a wide variety of criticisms have been put forward. These include accusations that the associations are weak and overestimated due to publication bias, that there are many inconsistencies between studies, that the associations are confounded by lifestyle factors, and that there has been inappropriate adjustment for adult size. Finally many studies report that the findings in singletons do not seem to be replicated in twins. While many of these issues have been resolved, some continue to form the basis of a lively dialogue and ongoing research. Nevertheless the research findings have important implications for clinical obstetric practice and maternal-fetal medicine
Fetal programming of the neuroendocrine response to stress: links between low birth weight and the metabolic syndrome
No full textThere is now substantial agreement that small size at birth is associated with increased rates of the metabolic syndrome (glucose intolerance, high blood pressure, and dyslipidaemia) and related pathologies including cardiovascular disease in adult life. Evidence is also emerging that suggests programming of hormonal systems in response to an adverse fetal environment may be one of the mechanisms underlying these long-term consequences of early life events. In particular, alterations in the neuroendocrine response to stress may play an important part. Recent research suggests that increased adrenocortical and sympathoadrenal responses are associated with small size at birth. Evidence from epidemiological studies shows that subtle alterations in these neuroendocrine systems appear to exert a powerful influence on the levels of cardiovascular risk factors including plasma glucose and lipid concentrations and blood pressure
Regulation of glucocorticoid receptor ? and ß isoforms and type I 11ß-hydroxysteroid dehydrogenase expression in human skeletal muscle cells: a key role in the pathogenesis of insulin resistance?
No full textGlucocorticoid excess frequently results in obesity, insulin resistance, glucose intolerance, and hypertension and may be the product of altered glucocorticoid hormone action. Tissue sensitivity to glucocorticoid is regulated by the expression of glucocorticoid receptor isoforms (GR? and GRß) and 11ß-hydroxysteroid dehydrogenase type I (11ßHSD1)-mediated intracellular synthesis of active cortisol from inactive cortisone. We have analyzed the expression of GR?, GRß, and 11ßHSD1 and their hormonal regulation in skeletal myoblasts from men (n = 14) with contrasting levels of adiposity and insulin resistance. Immunohistochemical, Northern blot, and Western blot analysis indicated abundant expression of GR? and 11ßHSD1 under basal conditions. The apparent Km and maximum velocity for the conversion of cortisone to cortisol were 440 ± 14 nmol/L and 75 ± 7 pmol/mg protein·h and 437 ± 16 nmol/L and 33 ± 6 pmol/mg protein·h (mean ± SEM; n = 4) in the presence and absence of 20% serum. Incubation of myoblasts with increasing concentrations of glucocorticoid (50–1000 nmol/L) resulted in a dose-dependent decline in GR? expression and a dose-dependent increase in GRß expression. 11ßHSD1 activity was sensitively up-regulated by increasing concentrations of glucocorticoid (50–1000 nmol/L: P < 0.05). Abolition of these effects by the GR antagonist, RU38486, indicates that regulation of GR?, GRß, and 11ßHSD1 expression is mediated exclusively by the GR? ligand-binding variant. In contrast, 11ßHSD1 was down-regulated by insulin (20–100 mU/mL: P < 0.01) in the presence of 20% serum, whereas incubation with insulin under serum-free conditions resulted in a dose-dependent increase in 11ßHSD1 activity (P < 0.05). Incubation with insulin-like growth factor I resulted in a similar pattern of 11ßHSD1 activity. Although neither testosterone nor androstenedione (5–200 nmol/L) affected 11ßHSD1 activity, incubation of myoblasts with dehydroepiandrosterone (500 nmol/L) resulted in a decline in 11ßHSD1 activity (P < 0.05). These data suggest that glucocorticoid hormone action in skeletal muscle is determined principally by autoregulation of GR?, GRß, and 11ßHSD1 expression by the ligand-binding GR? isoform. Additionally, insulin and insulin-like growth factor I regulation of 11ßHSD1 may represent a novel mechanism that maintains insulin sensitivity in skeletal muscle tissue by diminishing glucocorticoid antagonism of insulin action
The ratio of second to fourth digit lengths: a marker of impaired fetal growth?
No full textBackground: epidemiological studies showing that impaired fetal growth has long-term adverse health consequences have depended on crude measures of fetal growth such as overall weight or length. For future studies, there is a need to develop improved morphological markers of fetal growth which persist into adult life. Recent studies have suggested that the ratio of the length of the second finger relative to the length of the fourth finger (2D:4D ratio) is determined during fetal life and may be such a marker. Aims: to determine whether the 2D:4D ratio is associated with size at birth. Design: Cohort study. Subjects: 139 men and women born in Preston, Lancashire between 1935 and 1943. Outcome measures: Measurements of the 2D:4D ratio in palm prints. Results: men who had an above average placental weight and a shorter neonatal crown-heel length had higher 2D:4D ratios in adult life. Conclusions: these preliminary findings lend support to the hypothesis that the 2D:4D ratio is determined during fetal life
Does body mass index reflect percentage body fat and body fat distribution in low and high birth weight subjects?
No full textBackground: Birth weight has been linked to increased morbidity and mortality in later life, but the mechanisms are poorly defined. It is not clear if adults with low and high birth weights have different percent body fat and pattern of fat distribution, which are associated with health outcomes, including cardiovascular disease. The purpose of this study is to assess if the percentage body fat and its distribution within the body differ between adults with a low and high birth weight, after adjusting for BMI. Methods: A total of 29 men aged 65-72 y old were recruited randomly from a Hertfordshire cohort with known birth weight and divided into two groups: a low birth weight group (<6.5 lbs); and a high birth weight group (>9 lbs). Body composition was assessed using DEXA Hologic Delphin and the results were processed using software v12.2, and expressed as mean +/-standard error. Results: Compared to the high birth weight group the low birth weight subjects were shorter (1.72 +/- 0.02 v 1.78 +/- 0.02m; P=0.05) and lighter (79.44 +/- 2.17 v 88.80 +/- 3.42 kg; P = 0.02). The low birth weight group also had a greater % body fat (28.71 +/- 1.03 v 25.53 +/- 1.85%; NS) despite a lower BMI (26.76 +/- 0.50 v 28.00 +/- 1.17 kg/m2; NS). When adjusted to the same BMI (27.31 kg/m2) using ANCOVA, there was about 5% more body fat (29.32 +/- 1.03 v 24.77+/-1.15 %; P=0.006) and more centrally located fat (ratio of non limb/ limb fat, 1.53 +/- 0.05 v 1.34 +/- 0.06; P=0.03). Conclusion: At the same BMI, older adults with a low birth weight had relatively more body fat and more centrally distributed fat than those with a high birth weight. This suggests that BMI should not be indiscriminately used to assess adiposity in low and high birth weight adults. The results could also help explain the higher risk of cardiovascular disease associated with poor fetal growth
Estimation of baroreflex sensitivity during mental stress testing - a comparison of different methods
No full text- …
