The Effects of STZ-Induced IDDM on Neural Crest Cell Migration andNeuroepithelialCell Proliferation: An Immunohistochemical and Stereological Analyses Study.

Diabetes-induced congenital malformations commonly affect organs and tissues that are derived fromectomesenchymal cells, such as the neural tube and cardiovascular structures. Human diabetic pregnancy has also been strongly associated with DiGeorge anomaly, Goldenhar and the axial mesodermal dysplasia syndromes. The cellular and molecular mechanisms of these malformations are still poorly understood, including their effects on the migration and proliferationof the ectomesenchymal-derived cells. Diabetes (IDDM) was induced in female MF1 mice with 150mg/kg of Streptozotocin one week before mating. Pregnancy was terminated on E9.5. E10, E11 or E12 and the embryos were examined for gross structural malformations. The distributions of immunoreactivity for migrating neural crest cells, permissive ECM substrate molecules (fibronectin andlaminin) and proliferating cells were investigated in histological sections of the malformed embryos. The absolute number of migrated cells in the trigeminal ganglion was also stereologically estimated. It could not be deduced from the results that the diabetic milieu directly affected the migratory pattern of the cranial neural crest cells and ECM molecules along the migratory pathways. However, the proliferative cycle and interkinetic migration of neuroepithelial cells were distorted in the malformed embryos from the diabetic mice. An average deficit of 11.2%-13.5% in the estimated absolute number of cells in the trigeminal ganglion was also observed. It is probable that the teratogenic effects of the diabetic state involve inhibition of the developmental processes of ectomesenchymal cells,including progenitor cells' differentiation and cell proliferation, through interference with the expression of a variety of the cells'developmental regulating genes and molecules.

Key Words: Neural crest; Neuroepithelial; Cell migration; Proliferation; Congenital malformations