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Depletion of oocyte dynamin-related protein 1 shows maternal-effect abnormalities in embryonic development
Science Advances ( IF 11.7 ) Pub Date : 2022-06-15 , DOI: 10.1126/sciadv.abl8070
Deepak Adhikari 1 , In-Won Lee 1 , Usama Al-Zubaidi 1, 2 , Jun Liu 1 , Qing-Hua Zhang 1 , Wai Shan Yuen 1 , Likun He 1 , Yasmyn Winstanley 3 , Hiromi Sesaki 4 , Jeffrey R Mann 1 , Rebecca L Robker 1, 5 , John Carroll 1
Affiliation  

Eggs contain about 200,000 mitochondria that generate adenosine triphosphate and metabolites essential for oocyte development. Mitochondria also integrate metabolism and transcription via metabolites that regulate epigenetic modifiers, but there is no direct evidence linking oocyte mitochondrial function to the maternal epigenome and subsequent embryo development. Here, we have disrupted oocyte mitochondrial function via deletion of the mitochondrial fission factor Drp1. Fission-deficient oocytes exhibit a high frequency of failure in peri- and postimplantation development. This is associated with altered mitochondrial function, changes in the oocyte transcriptome and proteome, altered subcortical maternal complex, and a decrease in oocyte DNA methylation and H3K27me3. Transplanting pronuclei of fertilized Drp1 knockout oocytes to normal ooplasm fails to rescue embryonic lethality. We conclude that mitochondrial function plays a role in establishing the maternal epigenome, with serious consequences for embryo development.

中文翻译:

卵母细胞动力蛋白相关蛋白 1 的耗竭显示胚胎发育中的母体效应异常

鸡蛋含有大约 200,000 个线粒体,这些线粒体会产生三磷酸腺苷和卵母细胞发育所必需的代谢物。线粒体还通过调节表观遗传修饰因子的代谢物整合代谢和转录,但没有直接证据表明卵母细胞线粒体功能与母体表观基因组和随后的胚胎发育有关。在这里,我们通过删除线粒体裂变因子 Drp1 破坏了卵母细胞线粒体功能。裂变缺陷卵母细胞在植入前后发育过程中表现出高频率的失败。这与线粒体功能的改变、卵母细胞转录组和蛋白质组的变化、皮质下母体复合体的改变以及卵母细胞 DNA 甲基化和 H3K27me3 的减少有关。将受精 Drp1 敲除卵母细胞的原核移植到正常卵质中无法挽救胚胎致死率。我们得出结论,线粒体功能在建立母体表观基因组中发挥作用,对胚胎发育有严重影响。
更新日期:2022-06-15
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