Stage specific response of the mesenchyme to excess vitamin A in developing rat facial processes

The effects of excess retinol (vitamin A alcohol) on facial process formation were examined in cultured rat embryos. The embryos were explanted at day 11 of gestation (plug day = 0) and cultured for up to the 50-somite stage in rat serum containing added 1 microgram/ml or 10 micrograms/ml retinol. The reduction in outgrowth of facial processes was observed in 1-microgram/ml-retinol-treated embryos and this type of malformation was found to be more severe in 10-micrograms/ml-retinol-treated embryos. Histological findings of 10-micrograms/ml-retinol-treated embryos at the 50-somite stage showed that the nasal epithelium was developed but folded. In the mesenchyme, there were necrotic cells. Thymidine incorporation by mesenchymal cells of facial processes was determined. At the 50-somite stage, the uptake was decreased to 66.4% of control value at 1 microgram/ml retinol, whereas the addition of the same dose of retinol did not cause the inhibition at the 36-, 40-, and 42-somite stages. The uptake at the 50-somite stage was decreased to 23.0% as a result of the 10 micrograms/ml retinol treatment. Furthermore, the effects of cartilage-derived factor (CDF) on the facial mesenchyme were examined; 20 micrograms/ml of CDF stimulated the 3H-thymidine incorporation in facial mesenchyme, especially after the 42-somite stage. By the addition of 10 micrograms/ml retinol, the incorporation decreased to 45.7% at the 38-somite stage, but it did not decline with concomitant use of CDF after the 38-somite stage.(ABSTRACT TRUNCATED AT 250 WORDS)