Mechanisms of Thalidomide Embryopathy

Thalidomide caused severe congenital abnormalities, particularly limb defects, in over 10,000 babies in the 1950s and 1960s. The proposed mechanisms for its teratogenic effects include disrupted ubiquitin ligase function, oxidative stress, and anti-angiogenic effects. Thalidomide's disruption of the ubiquitin ligase complex impairs fibroblast growth factor expression, leading to impaired limb growth. Oxidative stress generated by thalidomide causes DNA damage in the embryo, downregulating limb growth signaling factors. Thalidomide also blocks the expression of angiogenic factors, hindering blood supply development and impacting fetal growth. These insights into the mechanisms behind thalidomide's toxicity contribute to our understanding of its effects and inform the use of thalidomide in other medical conditions, such as hereditary hemorrhagic telangiectasia and small intestinal angiodysplasia.