Ionizing radiation exposure during development and growth restriction in mammals

Abstract

Exposure of the developing offspring to high doses of ionizing radiation before birth can result in short- and long-term decreases in offspring growth and size, which is known as developmental programming. This outcome in particular is an area of concern, as developmental programming with other stressors has been reported to lead to adverse effects later in life for the offspring. This thesis studied the effects of ionizing radiation exposure during development in two mammalian models: beagle dogs and BALB/c mice. The role of different irradiation regimens (fractionated, protracted and pre-treatment with a low dose of radiation) on the offspring effects were a focus of this thesis. The effects of an acute 1.82 Gy x-ray irradiation during late gestation and a number of different irradiation treatments were studied in a mouse model, with evidence for radiation-induced growth restriction in irradiated offspring. The role of the placenta, which is an important regulator of mammalian growth and development was also investigated further, to provide novel insights into the dysregulation occurring within this tissue. A number of novel differentially expressed genes, and impacted cellular pathways were identified within the placenta using RNA-sequencing technologies. Overall, this thesis provides further evidence for radiation-induced growth restriction, with information on how this response can vary based on the irradiation schedule and timing of exposure. This information is important to develop future countermeasures with the goal of limiting the adverse effects of radiation exposure.