Increased mtDNA mutation frequency in oocytes causes epigenetic alterations and embryonic defects.
Increased mtDNA mutation frequency in oocytes causes epigenetic alterations and embryonic defects.
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卵母细胞 mtDNA 突变频率增加导致表观遗传改变和胚胎缺陷
DOI：
10.1093/nsr/nwac136
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发表时间：
2022-10
影响因子：
20.6
通讯作者：
中科院分区：
文献类型：
--
作者：
线粒体对于女性生殖过程至关重要，但是卵母细胞中线粒体DNA（mtDNA）突变的功能仍然难以捉摸。 POLGM卵母细胞显着，POLGM卵母细胞显示出受精的全球DNA甲基化；此外，重塑，代谢组分析确定了来自POLGM小鼠的卵母细胞的α-酮戊二酸（αkg）水平的显着降低卵母细胞MTDNA突变在胚胎发生过程中控制表观遗传重编程和基因表达的重要作用。
Mitochondria are essential for female reproductive processes, yet the function of mitochondrial DNA (mtDNA) mutation in oocytes remains elusive. By employing an mtDNA mutator (Polgm) mouse model, we found the fetal growth retardation and placental dysfunction in post-implantation embryos derived from Polgm oocytes. Remarkably, Polgm oocytes displayed the global loss of DNA methylation; following fertilization, zygotic genome experienced insufficient demethylation, along with dysregulation of gene expression. Spindle–chromosome exchange experiment revealed that cytoplasmic factors in Polgm oocytes are responsible for such a deficient epigenetic remodeling. Moreover, metabolomic profiling identified a significant reduction in the α-ketoglutarate (αKG) level in oocytes from Polgm mice. Importantly, αKG supplement restored both DNA methylation state and transcriptional activity in Polgm embryos, consequently preventing the developmental defects. Our findings uncover the important role of oocyte mtDNA mutation in controlling epigenetic reprogramming and gene expression during embryogenesis. αKG deserves further evaluation as a potential drug for treating mitochondrial dysfunction-related fertility decline.
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DOI：
10.1042/bj20130029
发表时间：
2013-10-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Fetterman JL;Zelickson BR;Johnson LW;Moellering DR;Westbrook DG;Pompilius M;Sammy MJ;Johnson M;Dunham-Snary KJ;Cao X;Bradley WE;Zhang J;Wei CC;Chacko B;Schurr TG;Kesterson RA;Dell'italia LJ;Darley-Usmar VM;Welch DR;Ballinger SW
通讯作者：
Ballinger SW
影响因子：
3.9
作者：
Lepikhov K;Zakhartchenko V;Hao R;Yang F;Wrenzycki C;Niemann H;Wolf E;Walter J
通讯作者：
Walter J
影响因子：
2.7
作者：
Caprioli A;Villasenor A;Wylie LA;Braitsch C;Marty-Santos L;Barry D;Karner CM;Fu S;Meadows SM;Carroll TJ;Cleaver O
通讯作者：
Cleaver O
影响因子：
9.8
作者：
Lozoya OA;Martinez-Reyes I;Wang T;Grenet D;Bushel P;Li J;Chandel N;Woychik RP;Santos JH
通讯作者：
Santos JH
影响因子：
30.8
作者：
Hill, Jahda H.;Chen, Zhe;Xu, Hong
通讯作者：
Xu, Hong