Human epidemiological observations and experimental animal studies have shown that size at birth is critical in determining life expectancy (1). The smaller the neonate the less likely it is to survive at birth and the more prone it is to adult-onset degenerative diseases like hypertension and Type 2 diabetes. These observations have led to the hypothesis that adult disease arises in utero, in part, as a result of tissue programming during suboptimal intrauterine conditions associated with impaired fetal growth (1). The main determinant of fetal growth is the placental nutrient supply to the fetus, which, in turn, depends on the size, morphology, blood supply and transporter adundance of the placenta and on the synthesis and metabolism of nutrients and hormones by the placenta itself (2). However, very few studies have examined placental programming per se. Environmental factors, such as nutrition, temperature and glucococorticoid concentrations, are known to alter the placental capacity for nutrient transfer in several species. In sheep and rats, both under- and over-nutrition affect placental size, morphology and abundance of glucose transporters (GLUT1 & 3), although the specific effects depend on the severity, duration and gestational age at the onset of the perturbation. When nutrient deprivation occurs throughout pregnancy, placental efficiency measured as the fetal to placental weight ratio increases even though both fetal and placental weight is reduced. Similar increases in placental efficiency are seen when placental and fetal growth are restricted by maternal glucocorticoid treatment during late gestation. In some small placentae, this increased efficiency is coupled with enhanced transfer of glucose and/or amino acids per unit placental weight, which may reflect elevated transporter abundance or a relative increase in the surface area for nutrient exchange (2,3). In addition, in sheep, undernutrition and glucocorticoid overexposure alter placental glucose consumption and reduce the absolute amount and proportion of uterine glucose uptake delivered to the fetus (4). These insults also change the placental handling of lactate and specific amino acids. Furthermore, ovine placental production and metabolism of the eicosanoids and sex steroids are affected by uteroplacental nutrient availability and by fetal glucocorticoid concentrations during late gestation (5). Similarly, in rats and sheep, undernutrition and glucocorticoid treatment down-regulate the placental activity of 11β-hydroxysteroid dehydrogenase, the enzyme that inactivates glucocorticoids and limits feto-placental exposure to the higher maternal glucocorticoid concentrations (2). This increases glucocorticoid exposure and further compromises feto-placental development. The molecular mechanisms by which environmental signals alter placental nutrient transfer capacity remain unknown but many involve Igf2 and other imprinted genes (6). The Igf2 gene controls placental growth and its placental expression is down regulated in rodents by undernutrition and glucocorticoid treatment (3, 6). Disruption or deletion of the Igf2 gene either from all feto-placental tissues (complete null) or specifically from the labyrinthine trophoblast (Igf2P0 null) causes placental growth retardation and alters placental morphology with the result that the diffusion capacity and surface area for nutrient exchange are reduced (3, 7). Despite these changes, placental efficiency is increased in the Igf2P0 mutant compared to its wild type littermate (3). Measurements of unidirectional materno-fetal nutrient transfer have shown that the small Igf2P0 placenta transports more glucose and methly-aminoisobutyric acid (MeAIB) per gram than the wild type placenta in late gestation. These changes are accompanied by up-regulation of the Slc2a3 and Slc38a4 genes, which encode GLUT3 and an isoform of the System A family of amino acid transporters (7). None of these adaptations are observed in the small placenta of the complete Igf2 null (6). Indeed, the complete Igf2 null placenta is less efficient and transfers less MeAIB per gram than their wild type counterparts (7). The nutrient transfers capacity of the murine placenta is, therefore, responsive to the nutrient demands of fetal tissues still expressing Igf2 and regulated by the interplay between placental and fetal Igf2. In summary, the nutrient transfer capacity of the placenta is responsive to a range of environmental stimuli and to the genetic drive for fetal growth. Both nutritional and endocrine signals alter placental development and the ensuing phenotype although the molecular mechanisms involved have yet to be identified. Environmentally induced changes in the placental capacity for nutrient transfer have an important role in regulating fetal development and may either ameliorate or acerbate the programming effects of the insult on the fetus. Acknowledgements: We thank the BBSRC for funding.Reference 1 : Barker, DJP (1994) Mother, babies and disease. BMJ PublishingReference 2 : Fowden, AL. et al., (2006) J. Physiol 572, 5-15.Reference 3 : Angiolini E. et al., (2006) Placenta 27, S98-S102.Reference 4 : Ward JW. et al., (2004) J. Physiol. 554, 529-541.Reference 5 : Fowden AL. et al., (1994) Exp. Clin. Endo. 102, 212-221.Reference 6 : Fowden AL. et al., (2006) Horm. Res. 65, 49-57 Reference 7 : Constancia M. et al., (2005) PNAS 102, 19219-19224.