Postnatal development of uterine abnormalities in mice exposed to DES in utero

Postnatal development of uterine abnormalities was examined in the offspring of mice given 4 daily subcutaneous injections of 2,000 micrograms diethylstilbestrol (DES) and of oil vehicle alone from days 15 to 18 of gestation. The prenatally DES-exposed mice (DES mice) exhibited a disorganization of the inner circular musculature of the uterus as early as at 5 days of age. Invaginations of the luminal epithelium into the stroma which began to form in 5-day-old control and 10-day-old DES mice developed into uterine glands at 10 and 15 days, respectively. The number of glands per uterine section was significantly reduced in DES mice as compared with the controls at 10-30 days. Stratification with or without squamous metaplasia (ST) was found in the luminal epithelium of DES mice at 20 days. Five groups each of DES mice and the controls ovariectomized (OVX) at 10 days were given 5 daily subcutaneous injections of 10(-4), 10(-3), 10(-2), 10(-1), and 1 microgram 17 beta-estradiol (E2) starting at 25 days. ST was never observed in OVX mice given prepubertal injections of any E2 dose, whereas in DES OVX mice aged 30 days, ST was produced by prepubertal injections of E2 doses higher than 10(-2) micrograms/day. Uterine responsiveness, weight gain and gland formation were significantly reduced in DES mice given prepubertal E2 injections compared to the controls.