Numerous studies have established a link between oxidative stress and diabetic embryopathy7, 21, 22, 54. In Alx3-deficient embryonic cells, excess oxidative stress is a consequence of increased production of ROS, as well as of reactive nitrogen species evidenced by elevated nitrotyrosine content and expression of inducible NOS, which has been implicated in the pathogenesis of embryonic malformations induced by maternal diabetes43, 55.