Effects of Maternal Administration of Diethylstilbestrol and Estradiol on the Newborn Guinea Pig

Abstract

The subcutaneous injection of diethylstilbestrol (2.5 µg/day) into pregnant guinea pigs from the 28th or 40th day to term resulted in an accelerated tempo of differentiation of the genital tract of the female offspring at birth, as well as intense estrogenic stimulation. Estradiol (50 µg per day) injected over the same period caused insignificant estrogenic stimulation in the newborn. The normal embryogenesis of the genital tract is described and a pattern of caudocranial differentiation identified. The normal genital tract is described as a basis for the analysis of results in the newborn. Comparative studies in other animals are discussed.

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

“…As in normal animals subjected to the changing hor monal levels of the estrous cycle or in hyperstimulatory states as in pregnancy [1], the abnormal changes in the genital tract of severely affected DES-exposed animals showed a 'gradient' of alterations along its length. In the animals showing 'early' changes the gradient was repre sented by higher stimulatory effects at the vaginal level, intermediate ones at the cervical level and least at the endometrial level, the pattern of cellular changes, however, being authentic for each level.…”

“…recent or old, were absent in these animals. In the endocervix throughout the lower and upper segments [1], the basal cells were prom inent; they are usually absent in the upper segment. The superficial mucosa was also hyperplastic and thrown up into villi and folds; the overlying epithelium was thickened and heavily mucified.…”

“…The upper endocervical segment, immediately proxi mal to the endometrial junction, contains peculiar glands in the normal guinea pig [1], this being the only place in which glands are observed in the cervix. These transitional glands also showed characteristic changes in animals most severely affected after DES exposure ( fig.…”

“…4). The area involved was small but also extended into the transitional zone of the endocervix where there is normally an overlap of glands peculiar to this region and others of endometrial type [ 1 ]. Elsewhere throughout the length of the genital tract in such animals affected early, there was evidence of extreme estrogenic stimulation of the mucosal lining.…”

“…Many neoplastic effects were also observed but were more varied and in no instance duplicative of the clear cell carci noma of women: they were clearly determined by the tumor sensitivity of the animals used and were undoubt edly multifactorial in their genesis. Following the report of pronounced and specific effects of prenatal DES exposure on the genital tract of newborn guinea pigs [1], it was important to determine whether or not late or delayed effects might be observed in the off spring allowed to survive into adult life. This objective is realized in the present paper.…”