EFFECTS OF THALIDOMIDE ON PREGNANCY IN THE RABBIT.

Abstract

Pregnant adult cross-bred female rabbits of proven fertility were treated with daily doses of 300-500 mg thalidomide 100-200 mg phthaloyl-DL-isoglutamine or 200-400 mg DL-o-carboxybenzoyl-glutamic acid in order to determine the effects of these drugs on pregnancy. There were 53 experimental animals and 19 untreated doses. Drugs were a dministered as follows: 1) during the preimplantation stage Day 4 5 or 6; 2) during preimplantation and implantation Days 3-8 3-9 3-10 and 3-16; and 3) during the postimplantation period only Days 8-16. Progeny were examined as blastocysts fetuses (17-29 days) or pregnancy was allowed to go to term. Treatment with thalidomide restricted to the preimplantation stage showed morphological changes in all the blastocysts particularly in the embryonic disks. The offspring left to term developed into viable young but with some instances of minor skelet al abnormalities. In treated animals over the implantation stage (Days 3-8 9 or 10) there was a reduction in the number going to term and about 40% of these were malformed. A majority of the malformations were of a skeletal nature. Although implantation was delayed by thalidomide the number of implants was unaffected. The postimplantation survival rate was markedly affected. Phthaloyl-isoglutamine and carboxybenzoyl-g lutamic acid were only administered during the preimplantation period and consistent morphological effects on the blastocysts were absent. Litters allowed to go to term were unaffected.