2. Academic Validation
  3. Crosstalk between H3K4me3 and oxidative stress is a potential target for the improvement of ART-derived embryos

Crosstalk between H3K4me3 and oxidative stress is a potential target for the improvement of ART-derived embryos

  • Nat Commun. 2025 Dec 16. doi: 10.1038/s41467-025-67560-4.
Chuanxin Zhang # 1 2 3 4 5 6 7,  Hao Tian # 1 2 3 4 5 6 7,  Xiaoyu Yin # 1 2 3 4 5 6 7,  Xueqi Dong 1 2 3 4 5 6 7,  Ning Wang 1 2 3 4 5 6 7,  Yiwen Zhang 1 2 3 4 5 6 7,  Jiawei Wang 1 2 3 4 5 6 7,  Jinzhu Song 1 2 3 4 5 6 7,  Cheng Li 1 2 3 4 5 6 7,  Zi-Jiang Chen 1 2 3 4 5 6 7 8 9,  Boyang Liu 10 11 12 13 14 15 16,  Keliang Wu 17 18 19 20 21 22 23
Affiliations

Affiliations

  • 1 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China.
  • 2 National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China.
  • 3 Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China.
  • 4 Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China.
  • 5 Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China.
  • 6 Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, China.
  • 7 Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, China.
  • 8 Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
  • 9 Department of Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 10 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China. [email protected].
  • 11 National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China. [email protected].
  • 12 Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China. [email protected].
  • 13 Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China. [email protected].
  • 14 Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China. [email protected].
  • 15 Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, China. [email protected].
  • 16 Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, China. [email protected].
  • 17 State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China. [email protected].
  • 18 National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China. [email protected].
  • 19 Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China. [email protected].
  • 20 Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China. [email protected].
  • 21 Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China. [email protected].
  • 22 Shandong Key Laboratory of Reproductive Research and Birth Defect Prevention, Jinan, Shandong, China. [email protected].
  • 23 Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, China. [email protected].
  • # Contributed equally.
PMID: 41402350 DOI: 10.1038/s41467-025-67560-4
Abstract

With the advent and development of assisted reproductive technology (ART), more and more people affected by infertility have been able to obtain offspring successfully. Nevertheless, various adverse outcomes have been found to be associated with ART, and mechanisms behind them are still unclear. Therefore, in this study, we examine the differences between mouse pre-implantation embryos obtained via in vitro fertilization (IVF) and in vivo fertilization (IVO) at both transcriptional and epigenetic levels. We find remarkable H3K4me3 differences at blastocyst stage, which could be ascribed to the higher oxidative stress in IVF-derived blastocysts. Intriguingly, treatment with CPI-455, the inhibitor of KDM5 that catalyzes the demethylation of H3K4, successfully rescues the H3K4me3 signatures as well as transcription levels of several genes, facilitating embryo development in vitro and improving the pregnancy outcome. Consistently, CPI-455 supplementation also enhances the formation of high-quality human embryos, emphasizing the potential clinical application of CPI-455 in human ART.

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