DIFFERENTIAL-EFFECTS OF AN ANTISERUM TO EPIDERMAL GROWTH-FACTOR ON THE DEVELOPMENT OF TRANSPLANTED RAT EMBRYOS AND FETAL STRUCTURES IN-VIVO

In order to obtain information on the possible role of epidermal growth factor (EGF) in rat prenatal development, we tested the effects of a neutralizing antiserum to rat EGF and of recombinant human EGF on the growth and development of transplanted rat embryos and fetal structures. Ten-day embryos or 16-day fetal intestines (ileum and jejunum) or paws were transplanted under the capsule of both kidneys of young adult syngeneic host rats. Osmotic minipumps were used to infuse antiserum to rat EGF or normal rabbit serum (NRS) into the renal artery of the right kidney to ascertain direct effects on development. The transplants on the contralateral side served as internal controls. Infusion of the NRS did not affect growth of any of the fetal structures or of the embryo transplants. The antiserum to rEGF did not affect growth of the fetal ileum or paw transplants, but it inhibited growth of the fetal jejunum by 38%, and suppressed differentiation of hair follicles in the paws by approximately 90%. Tissue differentiation in the two segments of the intestine was unaffected by the antiserum. By contrast, growth of embryo transplants was stimulated by approximately 60% by the anti-EGF serum. Infusion of antiserum did not affect the growth of the -kidneys upon which the transplants were grown, and infusion of different doses of recombinant human EGF had no effect on growth of embryo transplants. Our data suggest that EGF may function as a negative growth regulator during the embryonic period, but it becomes a growth stimulator for specific tissues during the fetal period. These results are consistent with our previous findings with basic fibroblast and insulin-like growth factors in illustrating that the regulatory functions of growth factors may be more general during embryogenesis but they become more organ or tissue specific in the fetal period of development.