The effects of prenatal diethylstilbestrol (DES) exposure on the genitalia of pubertal Macaca Mulatta. I. Female Offspring

Nineteen pregnant female rhesus monkeys (Macaca mulatta) received 1 mg/day diethylstilbestrol (DES) over three time periods during gestation: day 21 to delivery (group I), day 100 to delivery (group II) and day 130 to delivery (group III). Seven females and five males of a total of 20 offspring are presently alive at 5 1/2 years of age; one female died at 5 years of age. No deaths have been shown to be treatment related. In female offspring, menstruation began at about 2 1/2 years of age, was irregular for approximately one and one-half to two years and then became regular. Vaginal ridging and/or cervical hooding have been observed in seven of the eight DES-exposed females, and three had histologically demonstrable vaginal adenosis. None of the anomalies was related to a specific treatment period, for they appeared in all treatment groups, nor did they occur in the age-matched controls. Furthermore, none of the animals, either treated or control, showed any evidence of adenocarcinoma. Therefore, exposure of Macaca mulatta females to DES in utero appears to be teratogenic, but thus far no carcinogenicity has been observed. Reports in humans indicate that adenocarcinoma is an additional manifestation of prenatal exposure to DES; also, treatment effects appear to be more commonly observed in individuals exposed during the early stages of gestation. From this viewpoint, the rhesus monkey is a potentially valuable model for the study of vaginocervical anomalies and adenosis, but it is premature to consider it a suitable model for the study of adenocarcinoma.