Study of nitric oxide implications in embryonic development and its shielding effects against teratogenicity

Abstract

Teratology has emerged as a modern science from its primitive descriptions in Vedic and Egyptian era due to its importance in animal development An agent or environment which is able to cause fetal abnormalities was termed as teratogen Josef Warkany whose work during 1940s showed that exogenous factors could induce congenital malformations is known as father of teratology Fetal abnormalities have become a serious concern considering the fact that out of 1314 million babies born every year worldwide approximately 5 of live births are reported to have birth defect s In the field of modern teratology thalidomide has its own contribution of several decades It represents an ideal teratogen as it produces minimal toxicity to the adults but a high degree of malformations in the embryos Despite being so infamous and controversial drug thalidomide is referred as wonder drug for its incomparable immuno-modulatory and antiangiogenic properties Resurrection of its clinical use has also benefited the field of oncology as well In recent clinical trials thalidomide or its analogs are being tested as an individual or in combinational therapy against several diseases Advancement in the technologies and informatics is helpful to generate and analyze large biological data sets omics data which are promoting a critical shift in the study of biomedical sciences In the present study omics data were used to profile the transcriptome of teratogenicity induced chick embryo Chick embryo model is well studied and widely accepted model for teratogenic studies Considering the fact that on 6th day of development the organogenesis of vital organs is completed in the chick embryo we chose to profile the transcriptome of whole embryo on 6th day under different experimental conditions There are more than 20 hypotheses put forward to explain mechanism of action of thalidomide and some of those are experimentally proven At proteins level there are few protein targets of thalidomide such as soluble guanylyl cyclase sGC cereblon tubulin and TBX5 However one of the significant signaling pathways of thalidomide mechanism of action is nitric oxide signaling via soluble guanylyl cyclase sGC newline