Maternal High-fat Diet Modulates Radiosensitivity of Hematopoietic Tissue in Male Offspring

Obesity is a growing global health concern, and the Western diet characterized by its high-calorie and high-fat content, is widely acknowledged as a major contributor. Obesity is closely linked to the onset of various metabolic syndromes in affected individuals. Furthermore, maternal obesity has been revealed to have persistent effects on the long-term health of offspring, a phenomenon widely recognized as the "developmental origins of health and disease" (DOHaD). In this study, we aimed to explore the potential modifying effects of maternal exposure to a high-fat diet (HFD) on the health outcomes of offspring after exposure to ionizing radiation. C57BL/6J female mice were fed either an HFD or a standard diet (STD) immediately after weaning at 3 weeks of age. At 10 weeks of age, they were mated with C3H/He male mice raised on an STD. The resulting pups were nursed by their dams and were subjected to a total body X-ray dose of 3.8 Gy at 7 days after birth. All pups were weaned onto an STD at 4 weeks of age, irrespective of their experimental group. Lifelong observation of these pups demonstrated that maternal exposure to HFD reduced the lifespan of male offspring postirradiation, whereas maternal HFD alone did not significantly impact the lifespan of both male and female offspring. Pathological analysis revealed that the lifespan shortening by maternal HFD after X irradiation was primarily attributed to early deaths associated with depletion of bone marrow cells and thymic lymphoma within 6 months after X irradiation. To the best of our knowledge, this is the first report showcasing the modifying effects of maternal HFD on the radiosensitivity of offspring.