Growth factors in preimplantation mammalian embryos

It has been hypothesized for some time that secretions of the oviduct and uterus are involved in stimulating cell proliferation in preimplantation mammalian embryos and promotion of early differentiation events that lead to successful implantation. At least some of the regulatory factors present within uterine secretions are growth factors that can act along a paracrine pathway by binding to specific receptors on embryonic cells. A list of polypeptide growth factors present in uterine tissues and fluids has been previously published by Brigstock et al. (1989) and along with those reported in this review, includes EGF, TGF-alpha, insulin, IGF-I, IGF-II, IGF-BPs, acidic and basic FGF, and CSF-1. The early embryo itself produces a number of growth factors and receptors. A summary of those covered in this review, including temporal aspects of their expression, is contained in Table 2.1. Most of the data are from studies on mouse embryos but where, possible, we have also included reports for other mammalian embryos. Taken together with the factors present in oviduct and uterine secretions, it is clear that preimplantation embryos reside in an environmental milieu in which they are exposed to growth factors of many kinds and that regulatory pathways at the autocrine, juxtacrine, and paracrine levels may all be operating. From a functional point of view, many of the factors we have reviewed have been shown to be able to enhance development when added to medium for culture of preimplantation embryos. The exact circuit or pathway and mechanism through which they exert their effects remain, for the most part, to be elucidated. None the less, a number of general features regarding growth factor function during preimplantation development have emerged. There appears to be a redundancy of gene products within several growth factor families, all of which can stimulate cell proliferative or metabolic events when added exogenously to preimplantation embryos in culture. Perhaps, then, in addition to functions of growth factors acting singly on their specific receptors, combinations of factors are important for induction of a specific developmental response. We have included many examples of synergistic actions of growth factors during preimplantation development in the previous sections. It is also possible that the result of combinations of factors may involve a process of interference whereby exposure of embryonic cells to one growth factor may compromise its ability to bind and respond to another.(ABSTRACT TRUNCATED AT 400 WORDS)