title: Glucocorticoid programming of intrauterine development.
abstract: Glucocorticoids (GCs) are important environmental and maturational signals during intrauterine development. Toward term, the maturational rise in fetal glucocorticoid receptor concentrations decreases fetal growth and induces differentiation of key tissues essential for neonatal survival. When cortisol levels rise earlier in gestation as a result of suboptimal conditions for fetal growth, the switch from tissue accretion to differentiation is initiated prematurely, which alters the phenotype that develops from the genotype inherited at conception. Although this improves the chances of survival should delivery occur, it also has functional consequences for the offspring long after birth. Glucocorticoids are, therefore, also programming signals that permanently alter tissue structure and function during intrauterine development to optimize offspring fitness. However, if the postnatal environmental conditions differ from those signaled in utero, the phenotypical outcome of early-life glucocorticoid receptor overexposure may become maladaptive and lead to physiological dysfunction in the adult. This review focuses on the role of GCs in developmental programming, primarily in farm species. It examines the factors influencing GC bioavailability in utero and the effects that GCs have on the development of fetal tissues and organ systems, both at term and earlier in gestation. It also discusses the windows of susceptibility to GC overexposure in early life together with the molecular mechanisms and long-term consequences of GC programming with particular emphasis on the cardiovascular, metabolic, and endocrine phenotype of the offspring.
authors.affiliation: Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK. Electronic address: alf1000@cam.ac.uk.
authors.forename: A L
authors.initials: AL
authors.lastname: Fowden
authors.affiliation: Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: O A
authors.initials: OA
authors.lastname: Valenzuela
authors.affiliation: Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: O R
authors.initials: OR
authors.lastname: Vaughan
authors.affiliation: Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK; Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, CA 90502, USA.
authors.forename: J K
authors.initials: JK
authors.lastname: Jellyman
authors.affiliation: Centre for Trophoblast and Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK; Department of Biological and Medical Sciences, Oxford Brookes University, Oxford, OX3 0BP, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Forhead
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development; D005938:Glucocorticoids / Q000378:metabolism*; D058751:Livestock / Q000502:physiology*; D011247:Pregnancy; D014599:Uterus / Q000502:physiology*
chemical_list: D005938:Glucocorticoids
keywords: Development; Fetus; Glucocorticoids; Placenta; Programming