Transcriptomic Analysis of Thalidomide Challenged Chick Embryo Suggests Possible Link between Impaired Vasculogenesis and Defective Organogenesis

• Published in: Chemical research in toxicology 2017-10, Vol.30 (10), p.1883-1896
• Main Authors: Veeriah, Vimal, Kumar, Pavitra, Sundaresan, Lakshmikirupa, Mafitha, Zeenath, Gupta, Ravi, Saran, Uttara, Manivannan, Jeganathan, Chatterjee, Suvro
• Format: Article
• Language: English
• Subjects: Animals; Chick Embryo; Gene Expression Profiling; Neovascularization, Pathologic - chemically induced; Neovascularization, Pathologic - genetics; Organogenesis - drug effects; Organogenesis - genetics; Thalidomide - administration & dosage; Thalidomide - toxicity
• ISSN: 0893-228X; 1520-5010
• DOI: 10.1021/acs.chemrestox.7b00199

Since the conception of thalidomide as a teratogen, approximately 30 hypotheses have been put forward to explain the developmental toxicity of the molecule. However, no systems biology approach has been taken to understand the phenomena yet. The proposed work was aimed to explore the mechanism of thalidomide toxicity in developing chick embryo in the context of transcriptomics by using genome wide RNA sequencing data. In this study, we challenged the developing embryo at the stage of blood island formations (HH8), which is the most vulnerable stage for thalidomide-induced deformities. We observed that thalidomide affected the early vasculogenesis through interfering with the blood island formation extending the effect to organogenesis. The transcriptome analyses of the embryos collected on sixth day of incubation showed that liver, eye, and blood tissue associated genes were down regulated due to thalidomide treatment. The conserved gene coexpression module also indicated that the genes involved in lens development were heavily affected. Further, the Gene Ontology analysis explored that the pathways of eye development, retinol metabolism, and cartilage development were dampened, consistent with the observed deformities of various organs. The study concludes that thalidomide exerts its toxic teratogenic effects through interfering with early extra-embryonic vasculogenesis and ultimately gives an erroneous transcriptomic pattern to organogenesis.