机构：[1]Center for Reproductive Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.[2]Shenzhen Key Laboratory of Gene Regulation and Systems Biology, Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.深圳市康宁医院深圳医学信息中心[3]BGI Genomics, BGI-Shenzhen, Shenzhen, China.[4]Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.[5]Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, China.[6]State Key Laboratory of Organ Failure Research, Department of Developmental Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, China.[7]Guangdong Key Laboratory of Construction and Detection in Tissue Engineering, Southern Medical University, Guangzhou, Guangdong, China.[8]Guangzhou Regenerative Medicine and Health Guangdong Laboratory (GRMH-GDL), Guangzhou, Guangdong, China.
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.
基金：
National
Key R&D Program of China (2018YFC1704300 to
Y.J.W.), the National Natural Science Foundation of
China (81070494 and 81170571 to G.Q.T,
81571442 to W.Z., and 31970589 to A.P.H.), the
Shenzhen Innovation Committee of Science and
Technology (JCYJ20200109141018712 to A.P.H.
and ZDSYS20200811144002008 to the Shenzhen
Key Laboratory of Gene Regulation and Systems
Biology and to A.P.H.), and the Stable Support Plan
Program of the Shenzhen Natural Science Fund
(20200925153035002 to A.P.H.)
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类|1 区生物学
小类|1 区生化与分子生物学1 区生物学
最新[2025]版：
大类|1 区生物学
小类|1 区生化与分子生物学1 区生物学
第一作者：
第一作者机构：[1]Center for Reproductive Medicine, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Yang Yang,Shi Liyang,Fu Xiuling,et al.Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state[J].PLoS biology.2022,20(6):e3001682.doi:10.1371/journal.pbio.3001682.
APA：
Yang Yang,Shi Liyang,Fu Xiuling,Ma Gang,Yang Zhongzhou...&Tong Guoqing.(2022).Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state.PLoS biology,20,(6)
MLA：
Yang Yang,et al."Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state".PLoS biology 20..6(2022):e3001682
生物学