Hematological and histological studies of the rabbit brachydactyly mutant were made to clarify the question of the blood abnormality that had previously been implicated in the teratogenic process leading to congenital amputation. The hemoglobin of fetal and adult br/br rabbits, studied by electrophoresis and cyanmethemoglobin assay, exhibited no differences from that of controls. The br/br fetuses were polycythemic and severely macrocytic. Fetal limb vessels showed thrombosis leading to hemorrhages in the extremities. The hepatic tissue was abnormal, being particularly poor in hematopoietic cells; blood cell macrocytosis was attributed to impaired erthropoiesis. Treatment of pregnant rabbits with folic acid plus vitamin B12 or with folinic acid was able simultaneously to prevent the fetal blood cell macrocytosis and the congenital abnormalities.

Mouse foetuses were treated by Thalidomide on days 11-12 in order to verify whether the drug would induce blood abnormalities leading to circulatory troubles. About 18% of the treated foetuses showed both severe limb haemorrhages on day 14, and obvious alterations of the nucleated red blood cells of vitelline origin. These blood abnormalities, occurring suddenly during the well-known 'critical stage' of foetal development, could be responsible for circulatory blocks leading to necrosis.

Pyrimethamine injected into the rat on days 12, 13, and 14 of gestation induces several types of malformations, including limb and facial deformities. These malformations appear in the same location as the hemorrhages and hematomas induced by this substance. In order to visualize the extent of the vascular disorders in the affected areas, a polymerizable substance was injected intravenously into the fetus. After pyrimethamine treatment, the fetal vascular network was simplified and reorganized in a different way according to the severity of the malformations. The appearance of vascular pathology, followed by malformations in the same regions, raises the hypothesis of a vascular cause of fetal defects.