修正的人三原核受精卵（corrected human three-pronuclear zygote，ch3PN）是指去除3PN中一个雄原核使其恢复为二倍体的受精卵。合子基因组激活（ZGA）失败是ch3PN发育阻滞的主要原因之一。DUX4是ZGA激活的关键因子，但其在ch3PN中调节ZGA的机制不清楚。我们前期结果表明组蛋白去甲基化酶KDM4A的过表达促进了DUX4基因的转录，进而使ch3PN的体外囊胚率显著提高，同时过表达KDM4A下调了H3K9me3和DNA甲基化水平。因此我们假设：KDM4A通过降低H3K9me3和DNA甲基化水平，上调DUX4基因的表达，促进ZGA的激活，从而提高ch3PN胚胎的发育潜能。本项目以ch3PN为研究对象，探究胚胎发育阻滞的原因，阐明KDM4A介导表观遗传修饰与DUX4调控ZGA的分子机制，为临床上不孕不育症的诊疗提供理论依据。

Corrected human three-pronuclear zygote (ch3PN) refer to the zygote that removes a male pronuclear from 3PN and restores it to diploid. Failure of zygote genome activation (ZGA) is one of the main causes of ch3PN developmental block. DUX4 is the key factor of ZGA activation, but its mechanism of action in ch3PN is not clear. Our previous results showed that the overexpression of histone demethylase KDM4A promoted the transcription of DUX4 gene, and significantly increased the in vitro blastocyst rate of ch3PN. Meanwhile, overexpression of KDM4A down-regulated H3K9me3 and DNA methylation in ch3PN. Therefore we make an assumption: KDM4A enhance the developmental potential of ch3PN embryos through reducing H3K9me3 and DNA methylation, up-regulating the expression of DUX4, and promoting ZGA. This project will take ch3PN as the research object, explore the molecular mechanism of KDM4A-mediated epigenetic modification and DUX4 regulation of ZGA, clarify the reasons for ch3PN embryo development block, and provide a theoretical basis for the diagnosis and treatment of clinical infertility.