PRODUCTION OF GROWTH FACTORS BY EARLY MAMMALIAN EMBRYOS

The roles of hormones and growth factors during the early stages of
mammalian development are poorly understood. During the past decade, it
has become apparent that embryos at several stages of development produce
growth factors, some of which exhibit the properties of transforming growth
factors (TGFs). TGFs are assayed by their ability to induce the soft agar
growth of non-transformed cells, such as normal rat kidney (NRK) cells.
The TGF-like growth factors from embryos were initially observed in
extracts prepared from mouse embryos at mid and late stages of gestation.
Recently, we have determined that embryos cultured from the blastocyst
stage release growth factors that induce the soft agar growth of NRK
cells. Although the precise developmental stage when production of these
factors begins has not been established, the data suggest that these
factors are released by cell types associated with early postimplantation
embryos. However, it has not been determined whether these factors are
released at earlier stages of development. Furthermore, the assay
employed, although relatively sensitive, could not unambiguously identify
the growth factors involved. This application proposes to address several
important questions concerning TGF-like growth factors released by early
mouse embryos: 1) What are their identities? 2) When are they first
produced? 3) Is their release modified by conditions that interfere with
development? 4) Are these factors produced by specific embryonic tissues?
These questions will be addressed by employing a battery of bioassays that
permit the identification of TGFs and related growth factors. The work
proposed in this application will help to clarify the roles of growth
factors during early development and help determine whether further study
of embryonic growth factors is likely to yield assays suitable for
monitoring normal preimplantation development.