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

Author:

Yang Yang,Shi Liyang,Fu Xiuling,Ma GangORCID,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.ORCID,Tong Guoqing

Abstract

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.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Shenzhen Science and Technology Innovation Commission

Publisher

Public Library of Science (PLoS)

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience

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