Effects of hypoxia on the embryogenesis of congenital vertebral malformations in the mouse.

With use of the mouse as the experimental animal and hypoxia as the teratogenic agent, the author produced congenital vertebral malformations identical in form to those found in man. Induced malformations were present in the cartilaginous stage of spine development. During the mesenchymal (prechondral) stage, two different phases of interaction occur between the matrix macromolecules (hyaluronate, glycosaminoglycans) secreted by the notochord and the sclerotomic cells. During the first phase, when the matrix is rich in hyaluronate, sclerotomic cells proliferate and migrate around the notochord in the control embryo. At the same time, in hypoxia-treated embryos, the author observed an inhibition of cell proliferation that was concomitant with a delay in reaching the normal concentration of hyaluronate. During the second phase, after the degradation of the hyaluronate complex, when the matrix is rich in free sulfated GAG, cell differentiation occurred around the notochord in control embryos. At this time, in the hypoxia-treated embryos the author found a delay in the liberation of sulfated GAG from the hyaluronate complex, which markedly changed the normal ratio between the sulfated GAG and nonsulfated GAG. He postulates that this delay in liberation of free sulfated GAG produces the asymmetrical (malformed) cartilage primum by asymmetrical cell differentiation.