Thalidomide, phthaloyl-dl-isoglutamine and dl-0-carboxybenzoyl-glutamic acid were administered orally to rabbits at different stages of pregnancy, at such a dose level that general maternal health, ovulation and fertilization did not appear to be affected.
When treatment with thalidomide was restricted to the pre-implantation period almost all the blastocysts were affected morphologically, particularly in the embryonic disks, but the majority developed into viable young, some of which, however, showed minor skeletal abnormalities. In one doe treated from Days 3 to 6 there was incomplete twinning. Continuation of thalidomide treatment over the time of implantation (Days 3 to 8, 9 or 10) or into later stages of pregnancy (Days 3 to 16 or 8 to 16) did not affect the number of embryos implanting, but the proportion going to term was reduced and about 40% of them were malformed. The majority of the malformations were associated with skeletal development and although some severe defects such as spina bifida and exencephaly were recorded, many of them were of a minor character and probably would not have affected the viability of the animal.
Phthaloyl-isoglutamine and carboxybenzoyl-glutamic acid were fed during the pre-implantation period only, and neither had any consistent morphological effect on the blastocysts. Litters allowed to go to term after treatment with the former were also unaffected.
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