A morphological and histochemical study of thalidomide‐induced upper limb malformations in rabbit fetuses

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Abstract
The upper limbs of 21‐day‐old thalidomide‐treated rabbit fetuses were studied macroscopically, histologically, and histochemically. The deformed limbs were arthrogrypotic, twisted, or medially rotated and inverted. Often these malformations were coupled with anomalies of the thumb. One or more of the preaxial bones or their primordia were either anomalous or missing. The degree of the induced dysmelia could be recognized by the graded severity of the histology. The least severely affected limbs exhibited defects of ossification and/or chondrification, whereas more severely affected ones contained atrophic chondrocytes, undifferentiated mesenchyme, or absence of primordia. In the deformed limbs glycogen was retained in the hypertrophic and calcified chondrocytes and glycogen granules were dispersed in reduced thenar structures, but alkaline phosphatase activity was reduced or absent in the same areas. There were no detectable differences in the amount or distribution of acid mucopolysaccharides between abnormal and control limbs. However calcium deposition in the cartilaginous matrices was reduced or absent in the abnormal limbs. In limbs with reduced amounts of osseous tissue there was no evidence of histochemical aberration in the deposited bone. It would appear, therefore, that thalidomide affected mesenchymal derivatives at various stages of development; that it was associated directly or indirectly with the utilization of glycogen and the production of alkaline phosphatase; and that its influence was expressed by aberrations in the chondrification and calcification processes during later fetal development.