Sea urchin embryos exposed to thalidomide during early cleavage exhibit abnormal morphogenesis later in development

Abstract

Background: Clinical use of thalidomide has increased drastically, pushing the questions concerning the teratogenic mechanisms of this drug back to the forefront. Progress in understanding the teratogenic mechanisms has been slow, with the lack of non-primate vertebrate animal models susceptible to the classic reduction deformities remaining a concern. Sea urchin embryos have been used as model organisms for developmental studies for the last century. Like vertebrates, they are deuterostomes and share similar developmental and signaling pathways suggesting they may be an effective system for thalidomide studies. Therefore, we tested sea urchin embryos to see if they were sensitive to the effects of thalidomide.

Methods: Sea urchin embryos were obtained using standard spawning and fertilization techniques. Thalidomide dissolved in DMSO was added to embryo cultures either at fertilization or during early cleavage. Samples of the embryos were evaluated during specific development stages.

Results: Lytechinus pictus embryos exposed to 400 microM thalidomide at fertilization or within a window during early cleavage (2-6 hours post-fertilization) exhibit significant levels of abnormal embryos (60-82%) at the pluteus stage, compared to controls levels (< or =10%). Strongylocentrotus purpuratus embryos exposed at initial fertilization or during early cleavage (2-6 hours post-fertilization) exhibit similar responses with significant abnormal levels ranging from (55-70%) at pluteus stage.

Conclusions: Both species of sea urchin tested were susceptible to thalidomide-induced teratogenesis during cleavage (4-16 cell stages). This response during cleavage stages warrants further study and indicates that sea urchin embryos may prove to be a useful tool for studying thalidomide effects early in development.