Aberrant H3K4me3 modification of epiblast genes of extraembryonic tissue causes placental defects and implantation failure in mouse IVF embryos.

Cell reports 2022 May 03

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Assisted reproductive technology has been widely applied in the treatment of human infertility. However, accumulating evidence indicates that in vitro fertilization (IVF) is associated with a low pregnancy rate, placental defects, and metabolic diseases in offspring. Here, we find that IVF manipulation notably disrupts extraembryonic tissue-specific gene expression, and 334 epiblast (Epi)-specific genes and 24 Epi-specific transcription factors are abnormally expressed in extraembryonic ectoderm (ExE) of IVF embryos at embryonic day 7.5. Combined histone modification analysis reveals that aberrant H3K4me3 modification at the Epi active promoters results in increased expression of these genes in ExE. Importantly, we demonstrate that knockdown of the H3K4me3-recruited regulator Kmt2e, which is highly expressed in IVF embryos, greatly improves the development of IVF embryos and reduces abnormal gene expression in ExE. Our study therefore identifies that abnormal H3K4me3 modification in extraembryonic tissue is a major cause of implantation failure and abnormal placental development of IVF embryos. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Dandan Bai, Jin Sun, Chuan Chen, Yanping Jia, Yanhe Li, Kuisheng Liu, Yalin Zhang, Jiqing Yin, Yingdong Liu, Xiaoxiao Han, Jingling Ruan, Xiaochen Kou, Yanhong Zhao, Hong Wang, Zheng Wang, Miaoxin Chen, Xiaoming Teng, Cizhong Jiang, Shaorong Gao, Wenqiang Liu. Aberrant H3K4me3 modification of epiblast genes of extraembryonic tissue causes placental defects and implantation failure in mouse IVF embryos. Cell reports. 2022 May 03;39(5):110784