Let-7 Derived from Endometrial Extracellular Vesicles is an Important Inducer of Embryonic Diapause in Mice

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2020 Sep 12

PMID 32917695

Citations 21

Authors

W M Liu

R R Cheng

Z R Niu

A C Chen

M Y Ma

T Li

P C Chiu

R T Pang

Y L Lee

J P Ou

Y Q Yao

W S B Yeung

Affiliations

Soon will be listed here.

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.

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