Role of the insulin-like growth factor system in uterine function and placental development in ruminants

Maternal nutrition during pregnancy influences fetal and placental weights. The insulin-like growth factors (IGF) are also important determinants of fetal size. Furthermore, the expression of several components of the IGF system is regulated by nutrition. Effects of nutrition on fetal growth could therefore be mediated by the IGF system in the uterus and placenta. The oviductal mucosa produces IGF-I, which may influence oviductal secretions or act directly on embryonic type 1 IGF receptors. In the uterus, IGF-I mRNA is localized to the stroma surrounding the endometrial glands, which contain high concentrations of IGF type 1 receptors. Uterine IGF-I concentrations fall during pregnancy; therefore, glandular activity is more likely influenced by systemic than local IGF-I production. The IGF-II mRNA is present in both caruncles and fetal placental mesoderm, but concentrations are much higher in the latter. The actions of IGF-I and IGF-II on the endometrium and placenta are influenced by IGF-binding proteins. In the ewe, mRNAs for IGF binding protein-1 and -5 are located in the luminal and glandular epithelia, IGF binding proteins-2 and -4 are produced in the subepithelial stroma, and IGF binding protein-4 is also in the placentome capsule; IGF binding protein-3 is more widely expressed in both maternal and fetal tissues. The IGF binding proteins, therefore, form a major barrier to the passage of IGF between the fetal and maternal circulatory systems.