Intrauterine growth retardation (IUGR), defined as impaired growth and development of the mammalian embryo/fetus or its organs during pregnancy, is a major concern in domestic animal production. Fetal growth restriction reduces neonatal survival, has a permanent stunting effect on postnatal growth and the efficiency of feed/forage utilization in offspring, negatively affects whole body composition and meat quality, and impairs long-term health and athletic performance. Knowledge of the underlying mechanisms has important implications for the prevention of IUGR and is crucial for enhancing the efficiency of livestock production and animal health. Fetal growth within the uterus is a complex biological event influenced by genetic, epigenetic, and environmental factors, as well as maternal maturity. These factors impact on the size and functional capacity of the placenta, uteroplacental blood flows, transfer of nutrients and oxygen from mother to fetus, conceptus nutrient availability, the endocrine milieu, and metabolic pathways. Alterations in fetal nutrition and endocrine status may result in developmental adaptations that permanently change the structure, physiology, metabolism, and postnatal growth of the offspring. Impaired placental syntheses of nitric oxide (a major vasodilator and angiogenic factor) and polyamines (key regulators of DNA and protein synthesis) may provide a unified explanation for the etiology of IUGR in response to maternal undernutrition and overnutrition. There is growing evidence that maternal nutritional status can alter the epigenetic state (stable alterations of gene expression through DNA methylation and histone modifications) of the fetal genome. This may provide a molecular mechanism for the role of maternal nutrition on fetal programming and genomic imprinting. Innovative interdisciplinary research in the areas of nutrition, reproductive physiology, and vascular biology will play an important role in designing the next generation of nutrient-balanced gestation diets and developing new tools for livestock management that will enhance the efficiency of animal production and improve animal well being.

The placenta is the organ that transports nutrients, respiratory gases, and wastes between the maternal and fetal systems. Consequently, placental blood flow and vascular development are essential components of normal placental function and are critical to fetal growth and development. Normal fetal growth and development are important to ensure optimum health of offspring throughout their subsequent life course. In numerous sheep models of compromised pregnancy, in which fetal or placental growth, or both, are impaired, utero-placental blood flows are reduced. In the models that have been evaluated, placental vascular development also is altered. Recent studies found that treatments designed to increase placental blood flow can 'rescue' fetal growth that was reduced due to low maternal dietary intake. Placental blood flow and vascular development are thus potential therapeutic targets in compromised pregnancies.

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Human adolescent pregnancy is characterized by poor pregnancy outcome; the risks of spontaneous miscarriage, prematurity, and low birth weight are particularly acute in girls who are still growing at the time of conception. Studies using a highly controlled sheep paradigm demonstrate that, in growing adolescents who are overnourished throughout pregnancy, growth of the placenta is impaired, resulting in a decrease in lamb birth weight relative to control-fed adolescents of equivalent age. Rapid maternal growth is also associated with increased spontaneous abortion rates in late gestation and a reduction in gestation length. Nutritionally sensitive hormones of the maternal somatotrophic axis may orchestrate nutrient partitioning in this paradigm and the particular role of growth hormone is discussed. At midgestation, the placentae of rapidly growing dams exhibit less proliferation in the fetal trophectoderm and reduced placental mRNA expression of a range of angiogenic factors. These changes occur before differences in placental size are apparent but may impact on subsequent vascularity. By late pregnancy, placental mass in the rapidly growing versus the control dams is reduced by approximately 45%; the fetuses display asymmetric growth restriction and are hypoxic and hypoglycemic. These growth-restricted pregnancies are associated with major reductions in absolute uterine and umbilical blood flows, leading to attenuated fetal oxygen, glucose, and amino acid uptakes. Placental glucose transport capacity is markedly reduced in the rapidly growing dams but is normal when expressed on a weight-specific placental basis. Thus, it is the small size of the placenta per se rather than alterations in its nutrient metabolism or transfer capacity that is the major limitation to fetal growth in the growing adolescent sheep. Information obtained from this highly controlled paradigm is clearly relevant to the clinical management of human adolescent pregnancies. In addition, the paradigm provides a robust model of placental growth restriction that replicates many of the key features of human intrauterine growth restriction per se.