Hypervitaminosis A dysmelia in rats.

Limb defects were induced in the offspring of rats by giving 200,000-800,000 i.u. per kg. vitamin A on days 10-16 of their pregnancy. The malformations were symmetrical and there was no fore or hind limb predominance but fore limb lesions tended to be more severe. As severity increased there was progressive distoproximal suppression of digital rays commencing with digits 1 and 5 then extending to digits 2 and 3. Digit 4 was affected last. Syndactyly of soft tissues and bone was a part of the process and could produce single composite digits. Deletion of digits occurred and could result from pure reduction defects or from syndactyly. The defect pattern and the sequence of digit involvement was fairly constant and matching patterns of reduction and fusion anomalies probably affected the carpal and the tarsal bones. Long bones showed varying degrees of shortening and deformity attributable to suppressed endochondral and periosteal bone formation. Repair phenomena following cessation of the treatment were in evidence. It is suggested that the skeletal malformations in the limbs result from first disturbed bone organogenesis and then from impeded postorganogenic bone growth.