Human zygotes are difficult to obtain for research because of limited resources and ethical debates. Corrected human tripronuclear (ch3PN) zygotes obtained by removal of the extra pronucleus from abnormally fertilized tripronuclear (3PN) zygotes are considered an alternative resource for basic scientific research. In the present study, eight-cell and blastocyst formation efficiency were significantly lower in both 3PN and ch3PN embryos than in normal fertilized (2PN) embryos, while histone H3 lysine 9 trimethylation (H3K9me3) levels were much higher. It was speculated that the aberrant H3K9me3 level detected in ch3PN embryos may be related to low developmental competence. Microinjection of 1000 ng/µl lysine-specific demethylase 4A (KDM4A) mRNA effectively reduced the H3K9me3 level and significantly increased the developmental competence of ch3PN embryos. The quality of ch3PN zygotes improved as the grading criteria, cell number and pluripotent expression significantly increased in response to KDM4A mRNA injection. Developmental genes related to zygotic genome activation (ZGA) were also upregulated. These results indicate that KDM4A activates the transcription of the ZGA program by enhancing the expression of related genes, promoting epigenetic modifications and regulating the developmental potential of ch3PN embryos. The present study will facilitate future studies of ch3PN embryos and could provide additional options for infertile couples.

中文翻译：

---

组蛋白去甲基化酶 KDM4A 过表达提高了校正的人三原核合子发育的效率

由于资源有限和伦理争论，人类受精卵很难用于研究。通过从异常受精的三原核 (3PN) 受精卵中去除额外的原核获得的经校正的人类三原核 (ch3PN) 受精卵被认为是基础科学研究的替代资源。在本研究中，3PN 和 ch3PN 胚胎的八细胞和囊胚形成效率均显着低于正常受精 (2PN) 胚胎，而组蛋白 H3 赖氨酸 9 三甲基化 (H3K9me3) 水平要高得多。据推测，在 ch3PN 胚胎中检测到的异常 H3K9me3 水平可能与发育能力低下有关。显微注射 1000 ng/µl 赖氨酸特异性去甲基化酶 4A (KDM4A) mRNA 可有效降低 H3K9me3 水平并显着提高 ch3PN 胚胎的发育能力。ch3PN 受精卵的质量随着分级标准、细胞数量和多能表达随着 KDM4A mRNA 注射的显着增加而提高。与合子基因组激活（ZGA）相关的发育基因也被上调。这些结果表明，KDM4A通过增强相关基因的表达、促进表观遗传修饰和调节ch3PN胚胎的发育潜力来激活ZGA程序的转录。本研究将促进未来对 ch3PN 胚胎的研究，并可能为不育夫妇提供额外的选择。响应 KDM4A mRNA 注射，细胞数量和多能表达显着增加。与合子基因组激活（ZGA）相关的发育基因也被上调。这些结果表明，KDM4A通过增强相关基因的表达、促进表观遗传修饰和调节ch3PN胚胎的发育潜力来激活ZGA程序的转录。本研究将促进未来对 ch3PN 胚胎的研究，并可能为不育夫妇提供额外的选择。响应 KDM4A mRNA 注射，细胞数量和多能表达显着增加。与合子基因组激活（ZGA）相关的发育基因也被上调。这些结果表明，KDM4A通过增强相关基因的表达、促进表观遗传修饰和调节ch3PN胚胎的发育潜力来激活ZGA程序的转录。本研究将促进未来对 ch3PN 胚胎的研究，并可能为不育夫妇提供额外的选择。促进表观遗传修饰和调节 ch3PN 胚胎的发育潜力。本研究将促进未来对 ch3PN 胚胎的研究，并可能为不育夫妇提供额外的选择。促进表观遗传修饰和调节 ch3PN 胚胎的发育潜力。本研究将促进未来对 ch3PN 胚胎的研究，并可能为不育夫妇提供额外的选择。