EFFECTS OF 1- -METHYLALLYLTHIOCARBAMOYL-2-METHYLTHIOCARBAMOYLHYDRAZINE (I.C.I. 33,828) ON EARLY PREGNANCY IN THE RAT

Publisher Website
Google Scholar
Abstract
Thirty-one virgin female rats in proestrus were mated with fertile males (Day 0). Groups of 4 to 6 animals were dosed by mouth with Compound ICI 33,828 (100 mg/kg) on 3 successive days starting, in different groups, on Days - 1, 0, 1, 2, 3 and 4, respectively. Twelve control rats were given the vehicle only. In all groups treatment with ICI 33,828 reduced the number of rats found pregnant at laparotomy, but in the treated animals found pregnant at laparotomy the mean number of implantation sites was not significantly different from that in the controls. In only one group, that dosed on Days 2 to 4, were no implantation swellings found in any animals. The results at autopsy showed that treatment resulted in heavy mortality of fetuses after implantation in those rats in which implantation occurred. In the control rats, 6.6% of the eggs shed were lost before the 6.6% after implantation. The corresponding figures for all the treated animals were 63.7 and 30.2%, respectively. Moreover, in the treated rats the development of the fetuses which survived to Day 19 was retarded, as judged by the size of the swellings on Day 8 or 11, and by the weight of the fetuses which at autopsy amounted on average to only two-thirds of that of the controls. In an experiment in which pseudopregnant rats were dosed with ICI 33,828 either before or before and after one horn of the uterus had been traumatized, it was found that the compound prevented the occurrence of a full deciduomal reaction. The effect was more marked when it was administered on Days 2 to 4 than on Days 4 to 6 of pseudopregnancy. From these results it was deduced that the compound might produce its antifertility effects of inhibiting pituitary function, thus upsetting the endocrine balance necessary for the maintenance of pregnancy.