Use of the neonatal mouse in studying long-term effects of early exposure to hormones and other agents.

The neonatal female mouse is considered as a model for studying the long-term consequences of exposure of the human fetus and neonate to hormones and other agents. Parallelism is noted between the results of administration of sex steroids and diethylstilbestrol (DES) to newborn mice and the phenomenon of vaginal cancer in young women whose mothers were given DES for threatened abortion. The progression of the neonatally steroid-treated mouse lesions from persistent vaginal cornification through hyperplastic lesions to tumors is described. The interaction of progesterone with estradiol is considered (lesions are fewer but more severe at 12 months of age following neonatal exposure to a combination of estradiol and progesterone), and the ability of neonatal progesterone treatment alone to result in cervicovaginal lesions in intact mice is emphasized. All steroids result in increased mammary tumor incidence and lowered age of tumor onset in intact mice bearing the mammary tumor virus; both the ovary and the virus are required for these effects. Possible ramifications of early perinatal exposure are indicated in regard to the male, to nongenital structures, to the endocrine system generally, and to immunologic mechanisms.