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.

胚胎滞育是一种母体控制的现象。控制这种现象发生的分子尚不清楚。我们证明，microRNA let-7a 的过度表达或与子宫内膜上皮细胞富含 let-7g 的细胞外囊泡一起孵育可延长小鼠囊胚的体外存活时间，这些囊胚在被转移到养母体内后发育成活的幼崽。与体内休眠囊胚相似，let-7诱导的休眠囊胚表现出低水平的增殖、凋亡和营养代谢。 Let-7 抑制 c-myc/mTORC1 和 mTORC2 信号传导以诱导胚胎滞育。它还抑制 ODC1 表达，减少多胺的生物合成，而多胺可以重新激活休眠胚胎。此外，let-7的过度表达会阻断滋养层分化和人类胚胎替代物的植入潜力，并延长人类囊胚在体外的存活时间，这支持了胚胎滞育是一种进化保守现象的观点。综上所述，let-7是诱导胚胎滞育的主要因素。