A study into the role of insulin and insulin-like growth factor I (IGF-I) in rat embryonic development.

Insulin, and the structurally related insulin-like growth factors (IGFs), are peptide growth factors believed to play a role in embryonic development. In addition to factors produced by the embryo, certain maternally derived growth factors may also be important during development. These are likely to act upon the extraembryonic membranes which surround the embryo throughout gestation, before they, or their breakdown products, are transported to the developing embryo. This thesis examines the processing of both insulin and insulin-like growth factor I (IGF-I) by the visceral yolk sac, an extraembryonic membrane in the rat. Both radiolabelled and fluorescently labelled ligands have been examined in 17.5 day yolk sacs, and their cultured equivalent. It appears that both factors are digested by this tissue very rapidly, which may involve receptor-mediated pinocytosis or surface digestion. Further, the role of the IGF-I receptor during rat embryonic development has been examined using a monoclonal antibody reported to block this receptor. When this antibody was applied to rat embryos cultured from 9.5 to 11.5 days of gestation, it resulted in growth retardation plus an associated increase in morphological abnormalities. These effects were largely reversed by the addition of an excess of IGF-I to the culture medium in the presence of this antibody, while the addition of insulin or IGF-II had no effect. In conclusion, receptors mediating insulin and IGF-I uptake appear to be present on the surface of the rat visceral yolk sac. The growth inhibition seen in the presence of the antibody also implicates that IGF-I plays a role in the normal development of post-implantation rat embryos.