Correlation of vertebral malformations with the synthesis and content of mucopolysaccharides during chondrogenesis.

Treating mice of strain C57BL/6Ffm on day 9 of gestation with 10 mg/kg of 5-fluoro-2'-deoxycytidine (FCdR) resulted in malformations of the thoracic vertebral column (ThVC) in 98% of near-term fetuses (Degenhardt et al., 1968). The spectrum of malformations was broad: fusion, dysplasia, cleft, aplasia and hypoplasia were all produced. Fusions of two or more segments represented more than half of all malformations (Bosse, 1978). The alterations in embryonic precartilage and cartilage after FCdR-treatment were followed from day 11 to day 15 in a biochemical and histological study. Biochemically, the 35S-uptake into embryonic mucopolysaccharides (MPS) and the content of total MPS and seven fractions of MPS in embryos or isolated ThVCs were analyzed. The histological variables studied were the types and incidence of malformations of the ThVC, 35S-autoradiography of the ThVC, and the amount of alcian blue-stained cartilaginous matrix. The results showed that on day 11 the synthesis of embryonic MPS was not affected, on day 12 the synthesis of MPS was greatly reduced, on day 13 the synthesis of MPS was slightly reduced while the MPS-content was not affected. On day 13 aplasias were seen in the same percentage as at term, but no fusions were detected. By day 14 the MPS-content was greatly reduced; hyaluronate, condroitin 4-sulfate, and chondroitin 6-sulfate being principally involved; the first fusions were seen. On day 15 the MPS-content was slightly reduced (chondroitin 6-sulfate and heparan sulfate were involved), fusions were complete. The results are discussed in terms of disturbance of structure and function of the notochord and intervertebral discs with the production of fusions, the main type of vertebral malformation in these experiments.