HIGH PH PREVENTS RETINOIC ACID-INDUCED TERATOGENESIS

Exogenously applied retinoic acid is known to cause teratogenic effect s in a variety of animal systems. We examined whether the formation of teratogenic effects may be influenced by the electrical charge of ret inoic acid. The pKa of retinoic acid ranges from 6 to 8, indicating th at it is electrically neutral in a pH5 medium and is negatively charge d in a pH9 medium. With th is idea in mind, embryos of the pond snail Lymnaea stagnalis were pulse-treated with retinoic acid and cultured i n media of different pH. The percentage of embryos with retinoic acid- induced eye defects was 6-fold lower in the pH9 medium as compared to the pH5 medium. In contrast, the apical plate defects induced by retin oic acid were not pH-dependent. The observation that high pH prevents eye defects but not apical plate defects can be explained by taking in to account an electrophoretic redistribution of retinoic acid resultin g from the voltage gradients that are generated by the Lymnaea embryo.