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. ~
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