Organ-Specific Mitochondrial DNA Copy Number Responses in Neonatal Mice Following in Utero Irradiation

Early-life ionizing radiation exposure may induce molecular responses without changes in birth outcomes. We examined whether in utero exposure to 0.2 Gy X-rays affects mitochondrial DNA copy number (mtDNAcn) and an index estimating the proportion of mitochondrial DNA (mtDNA) molecules amplifiable across a defined long region. Pregnant mice received sham irradiation or exposure on embryonic day 8 (E8) or 15 (E15). Offspring brain, heart, and liver were examined at birth, with litter means used as experimental units. Litter size and neonatal body weight showed no group differences. In organ-wise comparisons, brain mtDNAcn was higher after E8 and E15 exposure, heart mtDNAcn was higher after E15 exposure, and liver mtDNAcn showed no statistically detectable difference. Mixed-effects analysis supported an organ-dependent pattern of mtDNAcn responses, although direct E8-versus-E15 comparisons were not significant within any organ. The estimated proportion of long-fragment-amplifiable mtDNA was lower in the brain after E15 exposure in the organ-wise analysis, but mixed-effects analysis did not support organ- or gestational-stage-dependent patterns in this measure. Thus, in utero X-ray exposure produced organ-dependent mtDNAcn responses at birth but no demonstrable gestational-stage-specific response within individual organs.