Preliminary animal data at the Radiobiology Unit have shown an increase (about 20 to 30% per Gy) in the rate of exencephalies and more than 30% of eyes deffect when irradiating the pregnant mother at the organogenesis period (E8-E10). In some mice models, these malformations include mainly anencephaly, exencephaly, spina bifida and rachitisis (Juriloff and Harris, 2000). The more frequent NTDs is the exencephaly, where the foetus hasn’t a correct closure of the neural tube at the cranial area, which results in an absence of closure of the skull and an overgrowth of neural tissue in the region of the mid-brain. The link between NTDs and eye defect remain unknown.
Our investigations will essentially focus on radiation-induced teratogenicity effects and congenital anomalies (morphological and histopathological analyses). The ultimate objective is to illustrate the potential mechanisms (molecular pathways, metabolic processes and regulatory networks and epigenetics) leading to NTDs and brain anomalies and eyes defect resulting from an irradiation at the early post gastrula stages. Several microarray data have been generated the previous years after irradiation at the gastrula stage (within the FANC and NOTE EU project), and will be valorised by the PhD candidate to elucidate the early effects of radiation at the organogenesis period. The role of low vs. high folate diet will be studied, with particular emphasis on the early events just after the exposure and the late consequences leading to external malformations such as exencephaly/anencephaly and eyes defect.