The uterine growth-promoting action of epidermal growth factor and its function in the fertility of mice.

Epidermal growth factor (EGF) levels in the submandibular glands and plasma are increased in pregnant and aged female mice. The possible role of EGF in fertility was studied in virgin and pregnant mice ranging in age from 10 to 90 weeks of age, employing sialoadenectomy, administration of EGF antibody and EGF replacement. The uterine weight in pregnant, 10-week-old, sialoadenectomized mice was significantly less than in normal mice and the administration of EGF antibody to these mice further decreased uterine weight, resulting in an increased rate of abortion. Replacement EGF treatment in the sialoadenectomized mice prevented these changes. Uterine weight was about 70 mg at 10 weeks of age, and significantly increased from 30 to 80 weeks when it reached a plateau level of 275 mg. These changes closely followed the increase in the concentration of EGF in the submandibular glands and plasma and coincided with the decline in fertility. In contrast, uterine weight in the sialoadenectomized mice decreased immediately after the operation and remained at about 50-60 mg throughout the experimental period. Pregnancy, as judged by implantation, was achieved in the sialoadenectomized mice at later ages than in the controls. These findings suggest that elevated EGF levels may have a dual function in the control of fertility via uterine growth, depending on the age of mice.