Retinoids inhibit the differentiation of embryonic-mouse mesenchymal cells in vitro

The influence of all-trans retinoic acid, 13-cis retinoid acid and two aromatic retinoids (Ro 10-1670, Ro 11-1430) on the chondrogenic differentiation of mesenchymal cells in vitro was studied electron-microscopically. Organ cultures of limb buds from mouse embryos (Day 11) and high-density cultures of embryonic-mouse mesenchymal cells (Day 12) were used as experimental models. After a 6-day culture in the control medium, the development of hyaline cartilage was observed in both systems. In cultures which were treated with retinoids from Day 1 through Day 3 and then incubated in the control medium for 3 more days, the mesenchymal cells still maintained the morphological features of the blastema stage; cartilage synthesis was reduced (low retinoid concentrations) or completely absent (high retinoid concentrations). These findings indicate that the treatment of embryonic-mouse mesenchymal cells with retinoids induces a persistent and dose-dependent inhibition of chondrogenic differentiation, which in quantitative terms, is variably expressed during treatment with different retinoids. These inhibitory effects of retinoids on chondrogenesis are probably implicated in the pathogenetic mechanisms of their teratogenic action in vivo.