An attempt to quantify and evaluate the effect of in vitro fertilization on the genomic information of offspring
| Project/Area Number |
17K19913
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Health science and related fields
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| Research Institution | Kyushu University |
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Principal Investigator |
SAKUMI KUNIHIKO 九州大学, 生体防御医学研究所, 准教授 (50211933)
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| Co-Investigator(Kenkyū-buntansha) |
大野 みずき 九州大学, 医学研究院, 助教 (70380524)
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2018: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2017: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
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| Keywords | 生殖細胞突然変異 / 遺伝 / 体外受精 / ミューテーターマウス / ８-オキソグアニン / MTH1 / OGG1 / MUTYH / がんと遺伝 / 突然変異 / 生殖細胞 / 凍結保存 / エクソーム解析 / ゲノム障害 / 酸化ストレス |
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| Outline of Final Research Achievements |
The efficiency of in vitro fertilization and early development was significantly lower in the MTH1/OGG1/MUTYH triple knockout (TOY-KO) mice compared with wild type. This is considered to be due to an increased spontaneous mutation frequency in the germ lineage cells of the TOY-KO parent mice. To search the mouse strain with milder mutator phenotype, we prepared MTH1/OGG1, OGG1/MUTYH and MTH1/MUTYH double knockout mice, and MTH1, OGG1 and MUTYH single knockout mice in addition to TOY-KO mouse. By germline mutation analysis using whole exome sequencing, MTH1/MUTYH double knockout mouse showed decreased (about 1/10) mutation frequency with different mutation spectrum from TOY-KO mouse.
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| Academic Significance and Societal Importance of the Research Achievements |
2016年，我が国の全出生数に対する体外受精で生まれた子の割合は5.5%に達し，さらにその8割以上が凍結保存処置を経たものであった。これらの処置を経て生まれた体外受精児の約2%に何らかの異常の発生が報告されている。採卵，培養，凍結処置時に生じるゲノムへのダメージは一生涯，さらに子孫にまで引き継がれるものであり，その発生は極力抑制されなければならない。不妊治療に伴う次世代へのゲノムダメージの蓄積の実態解明を進め，その抑制方法を探すことは重要な課題である。
合わせて，ヒトの生殖・出産の適齢年齢は20歳～30歳であるという事実を広く知らしめ，不妊治療に頼らずにすむ社会環境構築の重要性を喚起したい。
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Fenton reaction-induced renal carcinogenesis in Mutyh-deficient mice exhibits less chromosomal aberrations than the rat model.2017
Author(s)
Li GH, Akatsuka S, Chew SH, Jiang L, Nishiyama T, Sakamoto A, Takahashi T, Futakuchi M, Suzuki H, Sakumi K, Nakabeppu Y, Toyokuni S.
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Journal Title
Pathol Int.
Volume: 67
Issue: 11
Pages: 564-574
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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