Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state

• Published in: PLoS biology Vol. 20; no. 6; p. e3001682
• Main Authors: Yang, Yang, Shi, Liyang, Fu, Xiuling, Ma, Gang, Yang, Zhongzhou, Li, Yuhao, Zhou, Yibin, Yuan, Lihua, Xia, Ye, Zhong, Xiufang, Yin, Ping, Sun, Li, Zhang, Wuwen, Babarinde, Isaac A., Wang, Yongjun, Zhao, Xiaoyang, Hutchins, Andrew P., Tong, Guoqing
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 30.06.2022; Public Library of Science (PLoS)
• Subjects: Arrests; Biology and Life Sciences; Cell cycle; Datasets; Embryonic development; Embryos; Epigenetic inheritance; Epigenetics; Gene expression; Genetic aspects; Genetic engineering; Glycolysis; Health aspects; Histones; In vitro fertilization; Metabolism; Morphology; Myc protein; Nicotinamide; Oxidative phosphorylation; Phenotypes; Phosphorylation; Physiological aspects; Resveratrol; Ribosomes; Stem cells; China
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3001682

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity. The arrested embryos can be divided into 3 types. Type I embryos fail to complete the maternal-zygotic transition, and Type II/III embryos have low levels of glycolysis and either high (Type II) or low (Type III) levels of oxidative phosphorylation. Treatment with the SIRT agonist resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype, which is accompanied by changes in metabolic activity. Overall, our data suggests metabolic and epigenetic dysfunctions underlie the arrest of human embryos.