Long-Term Responses of the Mouse Uterus to Neonatal Diethylstilbestrol Treatment and to Later Sex Hormone Exposure 1,2

ABSTRACT-The effects of ovariectomy at 1 month of age and continuous 17~-estradiol (E2) and/or progesterone (P) replacement on the uterus of BALB/cCrgl mice neonatally treated with diethylstil-bestrol [(DES) CAS: 56-53-1; a-a'-diethyl-4,4'-stilbenediol] or sesame oil were recorded after 1, 4, 7, and 10 months of treatment. DES-exposed uteri were found to be hypoplastic, less responsive to the growth-promoting effects of E2, and more likely to develop smooth muscle abnormalities after continuous hormonal treatment than similarly treated control uteri. Neonatal DES treatment led to leukocytic infiltration, disruption in the organization of the inner circular smooth muscle layer, and development of a population of epithelial cells believed to respond to later E2 treatment by proliferation and stratification (squamous metaplasia). Qualitative and quantitative responses to continuous P treatment and the development of cystic glandular hyperplasia and adenomyosis were