Let-7 derived from endometrial extracellular vesicles is an important inducer of embryonic diapause in mice
Open Access
- 11 September 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (37), eaaz7070
- https://doi.org/10.1126/sciadv.aaz7070
Abstract
Embryonic diapause is a maternally controlled phenomenon. The molecule controlling the onset of the phenomenon is unknown. We demonstrated that overexpression of microRNA let-7a or incubation with let-7g–enriched extracellular vesicles from endometrial epithelial cells prolonged the in vitro survival of mouse blastocysts, which developed into live pups after having been transferred to foster mothers. Similar to in vivo dormant blastocysts, let-7–induced dormant blastocysts exhibited low level of proliferation, apoptosis, and nutrient metabolism. Let-7 suppressed c-myc/mTORC1 and mTORC2 signaling to induce embryonic diapause. It also inhibited ODC1 expression reducing biosynthesis of polyamines, which are known to reactivate dormant embryos. Furthermore, the overexpression of let-7 blocked trophoblast differentiation and implantation potential of human embryo surrogates, and prolonged survival of human blastocysts in vitro, supporting the idea that embryonic diapause was an evolutionary conserved phenomenon. In conclusion, let-7 is the main factor inducing embryonic diapause.Keywords
Funding Information
- Foundation for Innovative Research Groups of the National Natural Science Foundation of China (NSFC 31471398)
- Research Grant Council , Hong Kong (GRF 17107915)
- National Key Basic Research Development Program (973 Program) from The Ministry of Science and Technology of the People’s Republic of China (MOST 2018YFC1004402)
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