Transplacental Action of Diethyistilbestrol on Reproductive and Endocrine Organs , Mammary Glands , and Serum Hormone Levels in Two-and Nine-Month-Old Female Rats 1

Aspects of morphology and endocrine function were studied in the reproductive tract and mammary glands of rats exposed prenatally to diethylstilbestrol (DES). Pregnant Sprague-Dawley rats received DES or vehicle on Days 15 and 18 of gestation. Female offspring exposed to DES or vehicle were assigned randomly to one of two experiments which differed in postnatal treatment. In Experiment 1, rats were intubateti with either 10 mg of 7,12-dimethylbenz(a)anthracene or vehicle at 50 days of age and sacrificed 1 week later. DES-exposed animals had significantly lower mean serum prolactin levels than did vehicleexposed controls at this age; 7,12-dimethylbenz(a)anthracene treatment did not affect this difference associated with DES exposure. The two exposure groups did not differ significantly with respect to (a) levels of serum estrogen or progesterone; (b) wet weight of the uterus, ovaries, or pituitary; or (c) microscopic appearance of the uterus, ovaries, vagina, cervix, pituitary, and adrenal glands. In the mammary glands, ductal tissue predomi nated in both exposure groups, but three of 32 DES-exposed animals showed some lobuloalveolar differentiation. In Experi ment 2, coincident with Experiment 1, rats from each exposure group were intubateti with 10 mg of 7,12-dimethylbenz(a)anthracene at 50 days of age or given two doses of 10 mg at Days 50 and 57 and sacrificed 7 months later. The DES-exposed rats at 9 months of age had significant reductions in body weight gain compared to vehicle-exposed controls; an increased inci dence of adrenal adenomata was observed among DES-exposed rats. No DES-associated differences were found with respect to serum prolactin; the wet weights of the uteri, ovaries, or pituitaries; the estrogen binding capacities of uterine cytosol; or the incidence of squamous metaplasia in uterine glands. In both exposure groups, there was variation in the morphology of the mammary gland and ovaries. Vaginal cytology at sacrifice con firmed that DES-exposed rats had similar proportions of animals in the different stages of the estrus cycle. The persistent vaginal cornification and increased incidence of other reproductive tract abnormalities (e.g., vaginal adenosis and gonadal hypogenesis) associated with neonatal estrogenization in rodents were not observed in rats exposed prenatally to this low dose of DES during the third week of gestation. Thus, the Sprague-Dawley rat is a useful model system in which to study the effects of 1This work was supported in part by Grant CA-18458 from the National Cancer Institute (USPHS), Grant RR-07064 from the NIH BiomÃ©dicalResearch Program, and Grant 11626 from the PSC-CUNY Research Award Program of the City University of New York. Support from the City University Research Project was used for the computer analysis of the data. 2To whom requests for reprints should be addressed, at Department of Biology, Queens College of City University of New York, 65-30 Kissena Blvd., Flushing, N. Y. 11367. Received October 5,1982; accepted June 30, 1983. prenatal exposure to low doses of DES on mammary gland development and carcinogenesis against a background of rela tively normal reproductive tract structure and function.