受胎前被ばくが導く次世代ミトコンドリアDNAの臓器特異的再編~ミトコンドリアゲノムから読み解く放射線の次世代影響~

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2026-02-04 北海道大学

北海道大学大学院保健科学研究院の福永久典准教授らは、妊娠前の放射線被ばくが次世代に及ぼす影響として、子どもの臓器ごとにミトコンドリアDNA量が変化することをマウス実験で明らかにした。脳や肝臓では、父母いずれの被ばくかに応じたミトコンドリアDNAコピー数の変化が認められた一方、心臓では有意な影響は見られなかった。また、肝臓ではミトコンドリアDNA量が少ないほど肝重量が大きい傾向があり、出生時の体重や臓器成長との関連も示された。本研究は、放射線の次世代影響をミトコンドリアゲノムの量的制御という新たな視点から捉えたものであり、放射線防護や健康リスク評価の高度化、放射線遺伝学の発展に寄与する基盤的知見となる。

受胎前被ばくが導く次世代ミトコンドリアDNAの臓器特異的再編~ミトコンドリアゲノムから読み解く放射線の次世代影響~
妊娠前の放射線被ばくは、子どもの臓器ごとにミトコンドリアDNA量を変化させ、出生時の体重や肝重量の増加と関連していたことを示す。

<関連情報>

受胎前被ばく後にみられるミトコンドリアDNAコピー数の世代間及び臓器特異的変化 Intergenerational and organ-specific alterations in mitochondrial DNA copy number following preconception irradiation

Ryosuke Seino, Hisanori Fukunaga
Redox Biology  Available online: 30 January 2026
DOI:https://doi.org/10.1016/j.redox.2026.104054

Highlights

  • Preconception irradiation is associated with acute mtDNA responses in parents.
  • Offspring exhibit intergenerational and organ-specific alterations in mtDNAcn.
  • No coordinated inter-organ mtDNAcn changes are observed in offspring.
  • Neonatal body and liver weight are increased across irradiated lineages.
  • Reduced hepatic mtDNAcn is associated with increased neonatal liver weight.

Abstract

Ionizing radiation, a potent inducer of redox stress, perturbs both nuclear and mitochondrial genomes, yet how such stress shapes mitochondrial inheritance across generations remains unclear. In this study, we examined intergenerational and organ-specific mitochondrial responses to parental X-ray irradiation in mice. Eight-week-old male and female C57BL/6N mice were exposed to 2 Gy of single whole-body X-ray irradiation before mating, generating paternal-, maternal-, and dual-irradiated lineages. In the parents, peripheral blood-derived mitochondrial DNA copy number (mtDNAcn) transiently increased one day after exposure, consistent with a rapid mitochondrial response to redox stress. In newborn offspring, mtDNAcn displayed clear organ- and parent-of-origin specificity: brain mtDNAcn decreased in paternal- and dual-irradiation lineages, heart mtDNAcn remained unchanged, and liver mtDNAcn showed the most pronounced depletion across all irradiated lineages. No significant inter-organ correlations in mtDNAcn were observed. All irradiated lineages exhibited increased body weight and increased liver weight at birth, with a significant positive association between these traits. Liver weight was negatively associated with hepatic mtDNAcn. Multiple regression analysis further showed that maternal pre-exposure mtDNAcn and offspring hepatic mtDNAcn independently predicted neonatal liver weight. Taken together, these findings demonstrate that preconception irradiation induces acute mitochondrial responses in parents and is associated with intergenerational, organ-specific mtDNAcn dysregulation that manifests as offspring birth outcomes. Parental irradiation perturbs organ-specific mitochondrial genome regulation and predisposes the next generation to altered growth-related traits.

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