2. Academic Validation
  3. Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state

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

  • PLoS Biol. 2022 Jun 30;20(6):e3001682. doi: 10.1371/journal.pbio.3001682.
Yang Yang 1,  Liyang Shi 2,  Xiuling Fu 2,  Gang Ma 2,  Zhongzhou Yang 3,  Yuhao Li 2,  Yibin Zhou 2,  Lihua Yuan 1,  Ye Xia 1,  Xiufang Zhong 1,  Ping Yin 1,  Li Sun 2,  Wuwen Zhang 1,  Isaac A Babarinde 2,  Yongjun Wang 4 5,  Xiaoyang Zhao 6 7 8,  Andrew P Hutchins 2,  Guoqing Tong 1
Affiliations

Affiliations

  • 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.
  • 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.
PMID: 35771762 DOI: 10.1371/journal.pbio.3001682
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.

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