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Evidence for the involvement of epidermal growth factor in fertility decline in aging female mice.

A decline in fertility, defined as the number of implantation sites, was observed in mice as they aged; the decline started at 30 weeks of age and reached a nadir by 60 weeks when no implantation was detected. Epidermal growth factor (EGF) levels in the submandibular gland and plasma increased as the female mice aged, and sialoadenectomy (surgical removal of the submandibular glands) attenuated the rise in the plasma EGF level without affecting the overall health or survival of the animals. Uterine weight at 10-20 weeks of age was about 70 mg, and it significantly increased with age. This weight has increased more than 2-fold by 60 weeks. These changes closely followed the increase in the concentrations of EGF in the submandibular gland and the plasma. After sialoadenectomy, uterine weight decreased immediately and remained at about 50-60 mg throughout the experimental period. Interestingly, sialoadenectomized mice became pregnant at an older age than the controls. These findings suggest that elevated levels of EGF may have a physiological role in fertility decline in aging mice perhaps via uterine hypertrophy.