Delay of human early development via in vitro diapause

Abstract

SUMMARY Many mammals can control the timing of gestation and birth by pausing embryonic development at the blastocyst stage. It is unknown whether the capacity to pause development is conserved, in general across mammals, and more specifically in humans. Activity of the growth regulating mTOR pathway governs developmental pausing in the mouse ( 1 ). Here we show a stage-specific capacity to delay the progression of human development via mTOR inhibition. In this context, human blastoids and pluripotent stem cells in naïve and naïve-like, but not primed, states can be induced to enter a dormant state, which is reversible at the functional and molecular level. Comparative analysis of mouse and human naïve cells’ longitudinal response to mTORi revealed distinct temporal dynamics and metabolic requirements of dormancy in each species. Mouse and human blastocysts show similar tissue-specific patterns of mTOR pathway activity, suggesting that the mTOR pathway may be a conserved regulator of blastocyst development and timing in both species. Our results raise the possibility that the developmental timing of the human embryo may be controllable, with implications for reproductive therapies.