The Biological Effects of Novel Synthetic Retinoids

Naturally occurring Retinoids are known to play a role in many developmental processes in the early embryo as well as being a potent tool for in vitro differentiation of stem cells. The exogenous application of these naturally occurring retinoids as well as some of their synthetic analogs has been shown to yield digit duplication phenotypes and facial phenotypes in the model system of chick. It is not however always appreciated that these naturally occurring retinoids are highly susceptible to isomerisation and that these isomers have different biological activity. Due to this EC23 and EC19, synthetic analogs of these retinoids which are not able to be isomerised, have been synthesized. These two compounds until now have not been tested in vivo. We showed that both EC23 and EC19 are able to yield retinoid phenotypes in the model system of chick. We also showed that EC23 is far more toxic than EC19 or ATRA, while being far more able to create retinoid limb phenotypes at lower concentrations. EC19 in this investigation is shown to produce very few retinoid limb phenotypes in comparison, but is able to yield a far higher frequency of retinoid facial phenotypes. In conclusion this investigation shows the ability of EC23 to emulate known ATRA limb phenotypes at much lower concentrations. EC19 is shown to yield less limb phenotypes possibly due to its similarities in structure to 13-cis RA, EC19 is also shown to yield facial phenotypes more frequently than EC23 or ATRA.