Abortifacient and teratogenic effects of triacetyl-6-azauridine in the monkey

Abstract

Triacetyl-6-azauridine, developed as an antineoplastic agent, has been shown to be highly embryotoxic in rodents. To test the abortifacient effect in an infrahuman primate where the entire pregnancy could be followed, the drug was given to macaque monkeys as soon as pregnancy was diagnosed (day 21 to 28 after insemination). In 14 pregnancies the treatment at different dosages induced 13 delayed abortions between the thirty-sixth and one hundred and thirty-first day. No correlation could be made between dosage, weight of animal, and time of abortion. One pregnancy carried to term when fetal dystocia required a hysterotomy, and a teratogenic male infant was delivered. A new approach was necessary to avoid teratogenesis and the delayed abortions. The drug was then given after insemination at the end of 50 menstrual cycles on days 27 to 30. This was thought to make possible the evaluation of its capacity to prevent pregnancy. Three pregnancies were identified and ended early in abortions on days 23, 24, and 30. Since one out of 5 matings in this colony usually results in pregnancy it is possible that other implantations were interrupted without overt evidence.