Programming of the stress response: a fundamental mechanism underlying the long-term effects of the fetal environment?
There is a large body of evidence which suggests that an adverse fetal environment results in a heightened biobehavioral 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.
Phillips
D I W
DI
MRC Resource Centre, Southampton General Hospital, University of Southampton, Southampton, UK. diwp@mrc.soton.ac.uk
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology; D002648:Child; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D007230:Infant, Low Birth Weight / Q000502:physiology; D007231:Infant, Newborn; D024821:Metabolic Syndrome / Q000209:etiology / Q000503:physiopathology; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology; D012307:Risk Factors; D013315:Stress, Psychological / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology
D000893:Anti-Inflammatory Agents; D006854:Hydrocortisone