Superovulation alters global DNA methylation in early mouse embryo development
Superovulation alters global DNA methylation in early mouse embryo development
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DOI：
10.1080/15592294.2019.1615353
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发表时间：
2019-05-12
期刊：
影响因子：
3.7
通讯作者：
Hawkins, R. David
中科院分区：
文献类型：
--
作者：
Yu, Bo;Smith, Thomas H.;Hawkins, R. David
已知辅助生殖技术在建立表观基因组的最活跃时期改变配子和早期胚胎的发育环境。这可能导致在主动DNA甲基化重编程期间引入错误。控制性超促排卵，或超排卵，是一种普遍使用的干预措施，已被证明可以改变某些印记基因的甲基化。本研究的目的是探讨卵巢过度刺激是否会导致小鼠早期胚胎全基因组DNA甲基化的变化。通过用低剂量（5 IU）或高剂量（10 IU）的PMSG和hCG处理小鼠来诱导卵巢过度刺激。自然交配（NM）对照小鼠不接受处理。从每组收集合子和8细胞胚胎，并通过全基因组亚硫酸氢盐测序产生DNA甲基化组。在NM组中，平均CpG甲基化水平从合子到8细胞期略有下降，而在两个超数排卵组中均观察到平均CpG甲基化水平大幅下降。对每个发育阶段内的平均CpG甲基化水平的单独分析证实，从受精卵到8细胞阶段的CpG甲基化的显著全基因组擦除仅发生在超数排卵组中。我们的研究结果表明，超数排卵改变了小鼠早期植入前胚胎的全基因组DNA甲基化擦除过程。目前尚不清楚这些变化是暂时的还是持久的。进一步的研究正在进行中，以调查卵巢过度刺激对胚胎发育后期DNA甲基化重建的影响。
Assisted reproductive technologies are known to alter the developmental environment of gametes and early embryos during the most dynamic period of establishing the epigenome. This may result in the introduction of errors during active DNA methylation reprogramming. Controlled ovarian hyperstimulation, or superovulation, is a ubiquitously used intervention which has been demonstrated to alter the methylation of certain imprinted genes. The objective of this study was to investigate whether ovarian hyperstimulation results in genome-wide DNA methylation changes in mouse early embryos. Ovarian hyperstimulation was induced by treating mice with either low doses (5 IU) or high doses (10 IU) of PMSG and hCG. Natural mating (NM) control mice received no treatment. Zygotes and 8-cell embryos were collected from each group and DNA methylomes were generated by whole-genome bisulfite sequencing. In the NM group, mean CpG methylation levels slightly decreased from zygote to 8-cell stage, whereas a large decrease in mean CpG methylation level was observed in both superovulated groups. A separate analysis of the mean CpG methylation levels within each developmental stage confirmed that significant genome-wide erasure of CpG methylation from the zygote to 8-cell stage only occurred in the superovulation groups. Our results suggest that superovulation alters the genome-wide DNA methylation erasure process in mouse early pre-implantation embryos. It is not clear whether these changes are transient or persistent. Further studies are ongoing to investigate the impact of ovarian hyperstimulation on DNA methylation re-establishment in later stages of embryo development.