Evidence for physiological function of epidermal growth factor: pregestational sialoadenectomy of mice decreases milk production and increases offspring mortality during lactation period.

Female virgin mice, whose submandibular glands were removed, underwent normal pregnancy and delivery. During the nursing period, however, a substantial number of pups born to and nursed by sialoadenectomized mothers died within 5 days of birth, whereas this did not occur among pups born to normal mothers. Cross-foster nursing experiments indicated that the cause of death of pups was to be found in sialoadenectomized mothers, not in the pups. The capacity of the sialoadenectomized mothers to nurse pups was much less than that of normal mothers, as shown by experiments involving alterations in the number of pups nursed by both sialoadenectomized and normal mothers. The mammary gland of lactating sialoadenectomized mice was smaller in size and produced less milk compared with that of normal mice. No apparent qualitative difference in milk proteins was found in the milk produced by the two groups of mothers. The decreased growth of the mammary gland of sialoadenectomized mice was also manifested during the second half of pregnancy, and mammary explants from those mice synthesized less casein in response to lactogenic stimuli, insulin, cortisol, and prolactin, in an organ culture system, when compared with mammary explants from normal pregnant mice. When epidermal growth factor, a polypeptide hormone that is synthesized and secreted by the submandibular gland, was injected daily at a dose of 5 micrograms into sialoadenectomized pregnant mice, the survival rate of the pups nursed by their mothers increased to the value obtained with normal mothers. The results were discussed in terms of a possible role of the submandibular gland and epidermal growth factor in the development of the mammary gland.