VAGINAL ADENOSIS AND ADENOCARCINOMA IN MICE EXPOSED PRENATALLY OR NEONATALLY TO DIETHYLSTILBESTROL

  • 1 January 1982
    • journal article
    • research article
    • Vol. 42  (5) , 2003-2011
Abstract
The association of intrauterine exposure to diethylstilbestrol (DES) and the subsequent development of reproductive tract abnormalities in young women has been well documented. Although the incidence of vaginal adenocarcinoma was low in the exposed population, vaginal adenosis, a nonmalignant abnormality, was quite common. To study the pathogenesis of adenocarcinoma and to determine the frequency of adenosis following prenatal exposure to DES, timed pregnant CD-1 mice were treated s.c. with DES (dose range 5-100 .mu.g/kg per day) on days 9-16 of gestation. This period corresponds to major organogenesis of the reproductive tract in the mouse. Female offspring were sacrificed at 1-18 mo. of age. In addition to nonmalignant abnormalities, some of which were described in women exposed prenatally to DES, 2 cases of vaginal adenocarcinoma (2%) were observed in 91 prenatally DES-treated animals. No comparable epithelial lesions were seen in 158 control female mice. One other case of adenocarcinoma of the vagina was reported previously by this laboratory using the prenatally exposed animal model. In another series of mice treated prenatally with DES, 100 .mu.g/kg per day, 3 of 20 (15%) 1 mo. old animals and 1 of 10 (10%) 18 mo. old treated offspring had glandular epithelium abnormally located in the vaginal fornices (adenosis). Other cervicovaginal abnormalities observed after prenatal DES exposure included structural alterations, cervical enlargement, squamous metaplasia in the endocervical canal, excess keratinization of the ectocervix and vagina, transverse folds and basal cell hyperplasia in the upper vagina and prominent Wolffian duct remnants. Vaginal adenosis in the mouse does not appear to be a common abnormality following treatment with DES in utero. Neonatal exposure to DES on days 1-5, on the other hand, resulted in 6 of 8 (75%) animals with adenosis at 35 days of age. Since perinatal mouse studies have reported high incidences of vaginal adenosis but no apparent cases of vaginal adenocarcinoma, the stage of cellular differentiation at the time of DES exposure may be critical in the final expression of these abnormalities.