胎内被ばくが導くミトコンドリアDNAの次世代変化~見た目では捉えられない”隠れた次世代影響”を明らかに~

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2026-04-09 北海道大学

北海道大学大学院保健科学研究院の研究チームは、妊娠初期の放射線被ばくが母体と胎児のミトコンドリアDNA(mtDNA)に与える影響を解析し、次世代への「隠れた影響」を明らかにした。マウスモデル実験により、mtDNAの変化が線量依存的に生じ、特に仔では母体よりも低線量からコピー数増加が確認された。一方で体重や性比などの外見的指標には変化が見られず、従来の評価では検出できない影響の存在が示唆された。本成果は、放射線の次世代影響評価に新たな視点を提供し、より精緻なリスク評価や防護基準の高度化に貢献する基盤的知見である。

胎内被ばくが導くミトコンドリアDNAの次世代変化~見た目では捉えられない”隠れた次世代影響”を明らかに~
妊娠初期の放射線被ばくは、母体には高線量でmtDNAの量的増加と正常コピー比の低下をもたらす一方、仔にはより低線量からmtDNAコピー数の増加をもたらす。

<関連情報>

受胎内放射線被ばくによる母体及び次世代のミトコンドリアDNA変化 Mitochondrial DNA alterations in mothers and offspring following in utero exposure to ionizing radiation

Ryosuke Seino, Haruka Kubo, Atsuko Ikeda, Hisanori Fukunaga
Free Radical Biology and Medicine  Available online 27 March 2026
DOI:https://doi.org/10.1016/j.freeradbiomed.2026.03.065

Highlights

  • In utero X-ray exposure at GD8 yielded live offspring at doses ≤0.5 Gy.
  • Maternal mtDNAcn rose at 2 Gy, while the intact mtDNA ratio fell at ≥0.5 Gy.
  • Offspring showed elevated mtDNAcn at ≥0.2 Gy without growth changes.
  • A consistent inverse relationship was observed between mtDNAcn and integrity.

Abstract

Ionizing radiation can perturb mitochondrial homeostasis and genomic stability, yet its developmental consequences remain insufficiently understood. We investigated how in utero X-ray exposure may affect mitochondrial DNA (mtDNA) regulation and developmental parameters in a mouse model. Pregnant C57BL/6N mice were exposed to 0 (sham-irradiated), 0.05, 0.2, 0.5 and 2 Gy X-rays at gestational day 8, corresponding to the onset of organogenesis. In maternal peripheral blood, mtDNA copy number (mtDNAcn) increased at 2 Gy, while the intact mtDNA ratio, defined as the degree of mtDNA homoplasy estimated by long-fragment PCR, decreased at ≥ 0.5 Gy. Pregnancy resulted in live offspring at GD8 X-ray doses of 0.5 Gy or lower. Offspring sex ratios and body weights did not differ between control and irradiated groups. Notably, offspring examined at two weeks of age exhibited significantly elevated mtDNAcn at ≥ 0.2 Gy, whereas intact mtDNA ratios were unchanged. These results demonstrate that in utero X-ray exposure is associated with dose-dependent alterations in mtDNA regulation in both mothers and their offspring, with distinct sensitivities observed between maternal and offspring responses. These findings highlight mitochondrial responses to radiation exposure during early development and suggest that prenatal irradiation may influence mtDNA regulation, with potential implications for mitochondrial function later in life.

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