FETAL EFFECTS OF EPIDERMAL GROWTH-FACTOR DEFICIENCY INDUCED IN RATS BY AUTOANTIBODIES AGAINST EPIDERMAL GROWTH-FACTOR

We have used rats with epidermal growth factor (EGF) autoantibodies to study the role of EGF deficiency during perinatal development. The st udy was focused on organs known to contain EGF or its receptor. Compar ed with controls, the offspring of autoimmune rats had a higher perina tal mortality and a lower birth weight. The weight of the lungs was pa rticularly low in the offspring of EGF-immunized rats, and morphologic ally the lungs from the surviving pups seemed atelectatic and had alve olar duct dilatation, which indicates mild respiratory distress syndro me. Judged from immunohistochemical studies, the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The off spring of EGF-immunized rats had dry and wrinkled skin. The skin was t hin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight rati o was lower in pups from EGF-immunized rats. This difference was, howe ver, not significant (p = 0.07), but flow cytometric analyses showed a significantly lower proportion of the liver cells from newborn EGF-de ficient pups to be in S-phase and indicated that these cells were larg er than liver cells from controls. To study possible alterations in EG F binding, I-125-EGF was injected i.v. in newborn rats. I-125-EGF boun d in all the organs investigated. The binding is listed in decreasing order: liver, gut, skin, kidney, and lungs. In the pups from EGF-immun ized rats, the lungs and the skin bound a significantly higher amount than the controls. This could represent an upregulation of the EGF rec eptor in response to the lack of EGF. Postnatally, the pups from EGF-i mmunized mothers grew faster and were on par with controls within 1 wk . We found no differences concerning tooth eruption, ear opening, and eye opening. In extension of present knowledge concerning the tissue l ocalization of EGF and its receptor and concerning the pharmacologic e ffects of EGF, our study demonstrates an effect of EGF deficiency. Thi s supports a role for EGF in the epigenetic regulation of the developm ent of the lungs, the skin, and the liver.