ROLES OF GROWTH-FACTORS DURING PERIIMPLANTATION DEVELOPMENT

Several growth factor ligand and receptor gene products have been show n to play roles during preimplantation mammalian development. Genes fo r insulin-like growth factors (IGFs), transforming growth factors (TGF s), fibroblast growth factor (FGF), platelet-derived growth factor (PD GF) and receptors for insulin, IGF, PDGF, TGF alpha and epidermal grow th factor (EGF) are expressed by early embryos of several species incl uding mouse, rat, cow and sheep. Roles of growth factors during early development have been demonstrated by addition of purified growth fact ors to culture medium or by molecular genetic techniques that interfer e with gene expression. In this way, it has been shown that successful development of the blastocyst is dependent on the action of epidermal growth factor (EGF) and leukaemia inhibitory factor (LIF). Recent exp eriments show that both UF and EGF stimulate secretion of urokinase-ty pe plasminogen activator (uPA) and gelatinase BI matrix metalloprotein ase-9 (MMP-9) in day 7 mouse blastocyst outgrowths, At the same time, tissue inhibitors of MMPs (TIMPs) are also expressed by embryonic, dec idual and uterine tissues during the implantation process. It appears that LIF may act directly car indirectly, by inducing the expression o f other cytokines, to regulate the temporal and spatial production and activity of proteases and protease inhibitors to create a favourable environment for implantation.