Abstract
Compared to popular teratogenesis subjects such as lethality, microcephaly and tumorigenesis, little has been reported on neurocristopathy, deficient epithelial-mesenchymal transition (EMT) and cardiovascular anomalies following maternal exposures to tritiated water (HTO) in mammals. In order to collect basic data on prevention and safety therapeutic applications in diseases regarding radiation, the biologically unique effects of HTO and gamma-rays exposure need to be evaluated. Here, pregnant rats in the experimental groups were given either a gamma-ray irradiation or a single intraperitoneal injection of HTO. We reported on the relationships between each full body maternal exposure and subsequently observed embryonic lethality, external malformations, and visceral malformations, especially of cardiovascular nature. We observed a high frequency of teratogenesis, especially cardiovascular and facial anomalies, in both treated groups. These results indicate sensitivity to gamma-rays exposure and HTO exposure of rat fetus leading to dysfunction of neural crest development in formation of neurocristopathy syndrome and neurocristopathy-induced HTO syndrome, respectively, and especially cardiovascular anomalies, including ventricular septal defects, tetralogy of Fallot, double outlet right ventricle, riding aorta, atrioventricular valve and septum defects, right aortic arch, coarctation of aorta and aortic arch anomalies. These types of cardiovascular anomalies are quite similar to those found in humans, termed DiGeorge syndrome and Aligellie syndrome, suggesting that gamma-rays and HTO may play a role in dysfunction of neural crest and formation of human neurocristopahty as well as cardiovascular anomalies. It is crucial to consider the their effects involving processes of cell killing and DNA damage, dysfunction of neural crest and epithelial to mesenchymal transition (EMT) on the formation of these syndromes. This animal model is expected to contribute in investigating the mechanism of such teratogenesis in human, as well as their relative biological effectiveness.
