Delayed Effects of Prenatal or Postnatal Exposure to Diethylstilbestrol in the Adult Female Guinea Pig

Abstract

Of 25 mature female guinea pigs exposed transplacentally to diethylstilbestrol (DES) for more than 20 days before term, 8 showed abnormal changes in the genital tract (stimulation of the epithelium and stroma, cystic glandular hyperplasia of the endometrial glands near the junction of the upper endocervix and endometrium) and 9 showed severe changes (cystic glandular hyperplasia of the endometrial glands throughout the corpus uteri and cornua, squamous metaplasia). Hyperkeratosis of the vulvar and nipple skin was also observed. No neoplastic changes were observed with one exception at 14 months in one ovary. Prenatal exposure to DES for less than 15 days before term or after birth for 3 days failed to result in abnormal changes in the adults. Prenatal exposure to estradiol for more than 20 days also was without effect in the adult, despite the higher tolerated doses given to the mothers. Cycling activity as judged by vaginal opening was abnormal in all experimental groups, suggesting a derangement of the pituitary-hypothalamic function not specifically related to DES exposure. It was concluded that there is a critical period of exposure of the Müllerian duct- and sinus-derived tissues with respect to the delayed effects of prenatal exposure to DES, which is estimated on the basis of embryological studies to range from the 28th to about the 45th day of gestation.

Developmental exposure to diethylstilbestrol alters uterine gene expression that may be associated with uterine neoplasia later in life

“…Perinatal exposure to DES also induced reproductive tract abnormalities in laboratory rodents including mice [8–12], rats [13, 14], hamsters [15] and guinea pigs [16]. For example, when mice were treated neonatally with 2 µg DES/pup/d (approximately 1000 µg/kg/d) for the first 5 d of life, greater than 90% developed uterine adenocarcinoma by 18 mo of age [10, 17]; the tumor incidence increased with increasing doses of DES [18].…”

Pregnancy-Associated Hyperkeratosis of the Nipple

“…23 Furthermore, hyperkeratosis of the nipple has resulted from administration of diethylstilbestrol to guinea pigs for more than 20 days before term. 24 Alternatively, this disorder may result from friction in women who develop breast enlargement during pregnancy and are somehow predisposed. Friction may also contribute to the chronicity of the lesions.…”