The main uterine vessels of pregnant rats were clamped on day 14 for 30, 60, or 90 min. The fetal death rate was increased by 60 or 90 min clamping, proportional to duration. Some surviving fetuses showed skeletal retardation, bilateral limb anomalies, and cleft palate when examined on day 21. As early as 3 h after declamping, edema was seen in the mesenchymal tissue of the limbplates, together with a marked dilatation of the fetal vessels. Later this tissue became necrotic. The necrotic changes also involved surrounding mesenchyme including developing bone, which resulted in the observed limb malformations. In addition large blisters and hematomas at the tip of the snout may have caused tongue displacement to such an extent that palate closure was mechanically impaired. The malformations thus apparently resulted secondarily from necrosis of mesenchymal tissues that had been fully differentiated. This pathogenesis may be a common one for various malformations after impairment of fetal nutrition in rats at this particular develop mental stage. ~
Pregnant mice, rats, and rabbits were treated orally with ergotamine during midgestation. In doses that affected maternal weight gain during treatment, ergotamine produced an increase in prenatal mortality in rats and evidence of fetal retardation in all three species. The results are discussed in connection with the vasoconstrictive action of ergotamine. A uterotonic effect may also be involved in the mechanism of action. No specific teratogenic activity was detected in any of the three species.
The teratogenic effects on the offspring of ferrets given single sc injections of mustine hydrochloride on various days of gestation is described and compared with a smaller series of rats treated at similar stages of embryonic development. Distinct qualitative differences in the teratogenic responses of the 2 species were demonstrated. The predominant defects in ferrets were anophthalmia produced during early gastrulation, and tail abnormalities produced at the head‐process stage; whereas in rats the major deformities were limb defects and cleft palate and these resulted from treatment at the stage of the paddleshaped forelimb. The advantages of the ferret as an additional species for teratogenicity studies is discussed and methods of providing a continuously breeding colony required for such studies are described.
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