Epidermal growth factor (EGF) has been implicated in the control of
embryonic development, but although
the receptor is expressed from an early stage, there is little evidence of
embryonic expression of EGF. In
order to investigate the role of maternally derived EGF during organogenesis,
rat embryos were explanted at
d 9.5 and cultured in serum depleted of low molecular weight molecules (retenate)
which was then
supplemented with EGF. Serum depleted of low molecular weight molecules by
prolonged filtration loses its
capacity to support normal embryonic development, possibly due to the loss of
growth promoting factors.
The addition of EGF to retenate significantly improved embryonic development with
a maximal effect at
8 ng/ml. The addition of an analogue of EGF, long EGF, to retenate also
caused a significant increase in
development, although at higher concentrations a decrease in its effect was
observed, possibly due to down
regulation of the EGF receptor. Therefore, embryos may be able to utilise
maternally derived EGF during
organogenesis. To test the effects of inhibiting the EGF receptor during
organogenesis, d 9.5 embryos were
cultured in the presence of tyrphostin 47, a specific EGF receptor inhibitor.
Tyrphostin 47 caused a
significant dose-dependent decrease in the development of embryos which was
also observed when tyrphostin
47 was injected into the vitelline circulation at d 11.5 to bypass the effects
of the yolk sac. These findings
suggest that the EGF receptor is essential for normal organogenesis and may
play a role in the control of
proliferation and differentiation. Although EGF is not expressed in the rat
embryo at this stage, maternally
derived EGF may be the ligand for the embryonic EGF receptor.