Uppsala university: Faculty of Medicine: Department of medical cell biology: Research: Ulf Eriksson: Diabetic Pregnancy: Neural Crest Cells
Neural Crest Cells
Neural crest cells are sensitive to teratogenic influences
We have recently studied the neural crest cells, a group of cells that
migrate from the opposing epithelial folds of the closing neural tube
in the back of the embryo to a number of positions inside the embryo.
These cells contribute to the development of several organs, the heart,
facial skeleton, thymus, parathyroid, adrenal medulla and the whole
peripheral nervous system [47].
Neural crest cells are needed for a normal development of the outflow region of the heart as well as for correct architecture of the large vessels connected to the heart.
We have studied the cells that migrate from the cranial (upper) part of the neural tube in the U rat and shown that these cells are sensitive to exposure to diabetes and high glucose levels [21, 48]. This teratological sensitivity manifests itself as increased rate of malformations of the facial skeleton and the heart in offspring of diabetic U rats [48]. This type of maldevelopment occurs also in human diabetic pregnancy, as a high rate of cardiac malformations [7], and in a specific syndrome, diGeorges syndrome [49].
Marked underdevelopment of the lower jaw (arrow)
in a fetus from a diabetic U rat (right) compared
with a normal fetus from a non-diabetic U rat (left).
We have shown that the neural crest-associated developmental disturbances can be diminished with antioxidant therapy, both in vivo and in vitro [21, 48]. Interestingly, other studies have reported that the neural crest cells also seem to be teratologically sensitive toward exposure for high doses of ethanol [50-53], antiepileptic compounds [54], and, possibly, thalidomide [55]. A common mechanism of damage for these different teratogens may be detectable in future work [56].
Major cardiac malformations in the form of large defects in the atrio-ventricular septa (ASD and VSD) in a fetus from a diabetic U rat (b, lower figure). Compare with normal heart from a normal U fetus (a, upper figure). RA and LA = right atrium and left atrium, RV and LV = right and left ventricle [48].