INTRAUTERINE GROWTH-RETARDATION AND FETAL LOSSES ARE CAUSED BY EPIDERMAL GROWTH-FACTOR DEFICIENCY IN MICE

The plasma concentration of epidermal growth factor (EGF) in female mice increases during pregnancy. Sialoadenectomy (surgical removal of the submandibular glands) on day 13 of gestation attenuates the rise in plasma EGF and significantly reduces the percent of live pups on day 19 of pregnancy to 80% compared with 95% for the control animals. EGF replacement therapy given to the sialoadenectomized mice successfully prevented this reduction in the percent of live pups on day 19. The average weight of the live fetuses from sialoadenectomized mothers was significantly lower than those from the control mothers, i.e., 1.00 +/- 0. 14 (SD) g vs. 1.13 +/- 0.07 g. The administration of anti-EGF antiserum to the sialoadenectomized mice further affected fetal viability; only 70% of the pups were alive on day 19, with a mean weight of 0.93 +/- 0.15 g. The mean weight of the fetal body and that of the liver caused by sialoadenectomy were similarly reduced, but the brain was not affected, which shows that the growth retardation was asymmetrical. These findings suggest that EGF plays a physiological role in fetal growth and that EGF deficiency may be a cause of asymmetrical intrauterine growth retardation, which might be due to uteroplacental dysfunction.