mTOR hypoactivity leads to trophectoderm cell failure by enhancing lysosomal activation and disrupting the cytoskeleton in preimplantation embryo
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Published:2023-11-30
Issue:1
Volume:13
Page:
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ISSN:2045-3701
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Container-title:Cell & Bioscience
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language:en
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Short-container-title:Cell Biosci
Author:
Ma Chiyuan, Li Qin, Yang Yuxin, Ge Lei, Cai Jiaxuan, Wang Juan, Zhu Maoxian, Xiong Yue, Zhang Wenya, Xie Jingtong, Cao Yujing, Zhao Huashan, Wei Qing, Huang Chen, Shi Junchao, Zhang Jian V., Duan Enkui, Lei XiaohuaORCID
Abstract
Abstract
Background
Metabolic homeostasis is closely related to early impairment of cell fate determination and embryo development. The protein kinase mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism in the body. Inhibition of mTOR signaling in early embryo causes postimplantation development failure, yet the mechanisms are still poorly understood.
Methods
Pregnancy mice and preimplantation mouse embryo were treated with mTOR inhibitor in vivo and in vitro respectively, and subsequently examined the blastocyst formation, implantation, and post-implantation development. We used immunofluorescence staining, RNA-Seq smart2, and genome-wide bisulfite sequencing technologies to investigate the impact of mTOR inhibitors on the quality, cell fate determination, and molecular alterations in developing embryos.
Results
We showed mTOR suppression during preimplantation decreases the rate of blastocyst formation and the competency of implantation, impairs the post implantation embryonic development. We discovered that blocking mTOR signaling negatively affected the transformation of 8-cell embryos into blastocysts and caused various deficiencies in blastocyst quality. These included problems with compromised trophectoderm cell differentiation, as well as disruptions in cell fate specification. mTOR suppression significantly affected the transcription and DNA methylation of embryos. Treatment with mTOR inhibitors increase lysosomal activation and disrupts the organization and dynamics of the actin cytoskeleton in blastocysts.
Conclusions
These results demonstrate that mTOR plays a crucial role in 8-cell to blastocyst transition and safeguards embryo quality during early embryo development.
Funder
National Key Research and Development Program of China National Natural Science Foundation of China Basic and Applied Basic Research Foundation of Guangdong Province the Strategic Priority Research Program of the Chinese Academy of Sciences the China Manned Space Flight Technology Project Chinese Space Station
Publisher
Springer Science and Business Media LLC
Subject
General Biochemistry, Genetics and Molecular Biology
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