Early foetal thrombosis induced by Thalidomide in mouse: Possible explanation for teratogenicity

Abstract

Mouse foetuses were treated by Thalidomide on days 11-12 in order to verify whether the drug would induce blood abnormalities leading to circulatory troubles. About 18% of the treated foetuses showed both severe limb haemorrhages on day 14, and obvious alterations of the nucleated red blood cells of vitelline origin. These blood abnormalities, occurring suddenly during the well-known 'critical stage' of foetal development, could be responsible for circulatory blocks leading to necrosis.

Letter to the Editor

“…Early fetal thrombosis in mice associated with red blood cells (RBCs) abnormalities has been reported as a possible explanation for thalidomide teratogenicity. 9 The modulation of expression of several adhesion molecules on different cells including platelets and RBCs has also been previously proposed. 4 In our case, DVT and pulmonary embolism developed three months after thalidomide initiation, in a patient with high aCL on repeated measurements.…”

Venous Ulcers of the Lower Limbs Due to Congenital Thalidomide-Related Valve Defect

“…2 Pseudoainhum could be considered a partial amputation, and it has been reported in association with vascular anomalies that may induce ischemia. 9 Other cases of pseudoainhum have been observed in many diseases responsible for vascular or neurological abnormalities. 10 The coexistence of the vascular abnormalities and leg ulcers could be coincidental, but we postulate that thalidomide may have affected the migration and development of the mesenchymal and endothelial cells that are the precursors of the venous valves.…”

Vertebrate embryos as tools for anti-angiogenic drug screening and function

“…Mice are fundamental for angiogenesis research, but unfortunately mice can respond differently upon exposure to antiangiogenic compounds compared to humans [127]. Perhaps the best known example is thalidomide where mice and rats appear to be insensitive or less sensitive to thalidomide with several studies reporting no skeletal abnormalities [128–130] though in some strains of mice thalidomide-induced damage has been observed [131,132]. Interestingly thalidomide exposure in late pregnancy in rats has been shown to cause brain damage in areas associated with autism in humans, and has been linked to blood vessel loss [133].…”