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Nutritionally-Mediated Placental Growth Restriction in the Growing Adolescent: Consequences for the Fetus

Abstract
Human adolescent pregnancy is characterised 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 mid-gestation, 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 which 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 which replicates many of the key features of human intrauterine growth restriction per se.

Key words: Conceptus • Developmental biology • Implantation • Placenta • Uterus

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