Epidemiological findings and experimental studies in animals have shown that individual tissues and whole organ systems can be programmed in utero during critical periods of development with adverse consequences for their function in later life. Detailed morphometric analyses of the data have shown that certain patterns of intrauterine growth, particularly growth retardation, can be related to specific postnatal outcomes. Since hormones regulate fetal growth and the development of individual fetal tissues, they have a central role in intrauterine programming. Hormones such as insulin, insulin-like growth factors, thyroxine and the glucocorticoids act as nutritional and maturational signals and adapt fetal development to prevailing intrauterine conditions, thereby maximizing the chances of survival both in utero and at birth. However, these adaptations may have long-term sequelae. Of the hormones known to control fetal development, it is the glucocorticoids that are most likely to cause tissue programming in utero. They are growth inhibitory and affect the development of all the tissues and organ systems most at risk of postnatal pathophysiology when fetal growth is impaired. Their concentrations in utero are also elevated by all the nutritional and other challenges known to have programming effects. Glucocorticoids act at cellular and molecular levels to alter cell function by changing the expression of receptors, enzymes, ion channels and transporters. They also alter various growth factors, cytoarchitectural proteins, binding proteins and components of the intracellular signalling pathways. Glucocorticoids act, directly, on genes and, indirectly, through changes in the bioavailability of other hormones. These glucocorticoid-induced endocrine changes may be transient or persist into postnatal life with consequences for tissue growth and development both before and after birth. In the long term, prenatal glucocorticoid exposure can permanently reset endocrine systems, such as the somatotrophic and hypothalamic–pituitary–adrenal axes, which, in turn, may contribute to the pathogenesis of adult disease. Endocrine changes may, therefore, be both the cause and the consequence of intrauterine programming.

The thyroid hormones, thyroxine (T₄) and triiodothyronine (T₃), are essential for normal growth and development of the fetus. Their bioavailabilityin uterodepends on development of the fetal hypothalamic–pituitary–thyroid gland axis and the abundance of thyroid hormone transporters and deiodinases that influence tissue levels of bioactive hormone. Fetal T₄and T₃concentrations are also affected by gestational age, nutritional and endocrine conditionsin utero, and placental permeability to maternal thyroid hormones, which varies among species with placental morphology. Thyroid hormones are required for the general accretion of fetal mass and to trigger discrete developmental events in the fetal brain and somatic tissues from early in gestation. They also promote terminal differentiation of fetal tissues closer to term and are important in mediating theprepartummaturational effects of the glucocorticoids that ensure neonatal viability. Thyroid hormones act directly through anabolic effects on fetal metabolism and the stimulation of fetal oxygen consumption. They also act indirectly by controlling the bioavailability and effectiveness of other hormones and growth factors that influence fetal development such as the catecholamines and insulin-like growth factors (IGFs). By regulating tissue accretion and differentiation near term, fetal thyroid hormones ensure activation of physiological processes essential for survival at birth such as pulmonary gas exchange, thermogenesis, hepatic glucogenesis, and cardiac adaptations. This review examines the developmental control of fetal T₄and T₃bioavailability and discusses the role of these hormones in fetal growth and development with particular emphasis on maturation of somatic tissues critical for survival immediately at birth.

The intrauterine conditions in which the mammalian fetus develops have an important role in regulating the function of its physiological systems later in life. Changes in the intrauterine availability of nutrients, oxygen, and hormones program tissue development and lead to abnormalities in adult cardiovascular and metabolic function in several species. The timing, duration, severity, and type of insult during development determines the specific physiological outcome. Intrauterine programming of physiological systems occurs at the gene, cell, tissue, organ, and system levels and causes permanent structural and functional changes, which can lead to overt disease, particularly with increasing age.

Many animal studies and human epidemiological findings have shown that impaired growthin uterois associated with physiological abnormalities in later life and have linked this to tissue programming during suboptimal intrauterine conditions at critical periods of development. However, few of these studies have considered the contribution of the placenta to the ensuing adult phenotype. In mammals, the major determinant of intrauterine growth is the placental nutrient supply, which, in turn, depends on the size, morphology, blood supply and transporter abundance of the placenta and on synthesis and metabolism of nutrients and hormones by the uteroplacental tissues. This review examines the regulation of placental nutrient transfer capacity and the potential programming effects of nutrition and glucocorticoid over‐exposure on placental phenotype with particular emphasis on the role of theIgf2gene in these processes.