A histological and histochemical study of the development of the sternum in thalidomidetreated rats

Abstract

The development of the sternum was studied in normal and thalidomide‐treated rat embryos and fetuses. Morphologically, the sternal abnormalities included: crowding of the sternocostal articulations, absence of sternebrae, “scrambled” sternebrae, paired sternebrae, torsion of the sternum, partially cleft sternums, and completely bifurcated sternums. These malformations were related to an abnormal rib pattern and to a delayed growth rate of the ribs and sternebral primordia. Histochemically, the distribution and relative amounts of glycogen, alkaline phosphatase, calcium, and ribonucleic acid were studied. In cartilage the degradation of glycogen and the activity of alkaline phosphatase were influenced by thalidomide. This resulted in increased storage of glycogen and a reduction or absence of alkaline phosphatase activity. These changes were reflected in the rate of deposition of the cartilage matrix, and were most notable at the hypertrophic cartilage stage. Calcification of the cartilage was delayed, indicating the retardation in matrix deposition. No changes were observed in the staining pattern of ribonucleic acid. The deposition and calcification of endochondral bone was delayed, possibly caused by the delay in chondrification rather than by a direct effect on the ossification mechanism. No changes were observed in the development of the intramembranous, subperiosteal bone.

Phenocopies.

“…Lenz hypertrophic chondrocytes of the sternebrae of thalidomide-treated rats (Globus and Gibson, 1968). These experimental findings fit in with the speculation that thalidomide might interfere with mobilization of embryonic glycogen, based on the correspondence between the distribution of embryonic glycogen in the embryo and the pattern of thalidomide malformations (Lenz, 1963).…”

Evaluation of the developmental toxicity of thalidomide using frog embryo teratogenesis assay?Xenopus (FETAX): biotransformation and detoxification

“…The malformations induced in X. laevis in this study are similar to those found in several other species, including rabbits, mice, and man [3,4,[34][35][36][37]. These abnormalities have included skeletal effects on vertebrae, ribs, cranium, hip, sternum, and tail, in addition to amelia, phocomelia, possible polydactyly, and generally poor ossification.…”

Anomalies of Cartilaginous and Ossified Axial Skeleton in Rat Fetuses Treated with Cyclophosphamide: Type, Frequency, and Stage Specificity

“…Two sternal anomalies, i.e., sternebral misalignment and bipartite sternum, each have a peak sensitivity on GD9. Globus and Gibson (1968) studied the normal development of the rat sternum from GD11 to GD19. The paired sternal anlagen first appeared before GD 14 as mesenchymal condensations immediately below the ventral ends of the ribs.…”