Long Term Effects of Low Dose Radiation Exposure During Late Gestation on Cardiac Metabolism and Oxidative Stress
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abstract
An adverse in utero environment can result in fetal programming that can manifest as diseases later in life. Ionizing radiation (IR) is known to cause detrimental fetal programming especially during organogenesis. High doses of radiation cause severe cellular damage that can lead to mortality, however, the physiological effects of low dose radiation are not fully understood. This study examines the effect of low to non‐lethal radiation exposure during late gestation on cardiac metabolism and oxidative stress in adult mice. Pregnant C57BL/6J mice were exposed to 50, 300, or 1000mGy of gamma radiation or were sham irradiated on gestational day 15. At 4 months of age, 18FDG uptake was observed using PET imaging as an indicator of cardiac glucose uptake. Western blot was used to determine changes in 4‐hydroxynonenal adduct formation, catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx) protein expression and catalase, SOD and GPx enzyme activity was measured. Both male and female irradiated pups had lower body weights when compared to the sham group. Female pups receiving 1000mGy in utero, demonstrated a significant increase in 18FDG uptake and increased glycogen storage compared to sham group. However, female pups receiving 50mGy IR did not show a significant difference in 18FDG uptake or glycogen storage when compared to sham. Male pups did not exhibit increased 18FDG uptake, however at 50 and 300mGy IR there was decreased glycogen storage compared to sham. The reduced/oxidized glutathione redox ratio, a marker of oxidative stress, was significantly decreased in the female 300mGy and 1000mGy groups compared to sham but there was no change in males. We conclude that non‐lethal doses of radiation during late gestation can alter glucose uptake and storage as glycogen as well as oxidative status in female off‐spring. These data provide evidence that non‐lethal doses of radiation during the third trimester alter cardiac metabolism later in life and sex may have a role in fetal programming.Support or Funding InformationThis work was funded by the Natural Sciences and Engineering Research Council of Canada (NSERC) and by our industry partner, Bruce Power.
