Pathogenesis of a Bisdiamine‐Induced Malformation Complex in Rat Resembling DiGeorge Syndrome

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  • Pathogenesis of a Bisdiamine-Induced Malformation Complex in Rat Resembling DiGeorge Syndrome

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ABSTRACT Administration of the antispermatogenic agent bis-diamine (N, N’-bis- (dichloroacety1)-1 , 8-octamethylenediamine) to pregnant rats produced a malformation complex resembling DiGeorge syndrome in man. The malformations consisted of hypoplasia or aplasia of the thymus, persistent truncus arteriosus, tetralogy of Fallot, aberrant subclavian artery and other cardiovascular anomalies, as well as hypoplasia of the parathyroid gland, thyroid gland, and the spleen. The malformation complex appeared with a high incidence when the drug was administered on day 9.5 or day 10 of gestation. Since the connective tissues of the thymus, aorticopulmonary septum, smooth muscles of the media of the aortic arch artery, and connective tissues of the parathyroid and the thyroid glands, are of neural crest origin, and since the time of their migration is around day 10 of gestation, we postulate that the action of bisdiamine might be involution of the migration of the neural crest cells and of its pathways. We further suggest from the findings of persistent atrioventricular canal and hypoplasia of the spleen, that the drug must have also affected the growth of mesenchymal cells, which originate from the endocardia1 epithelial cells.

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