A uterus-inspired 3D niche drives embryo development beyond implantation

Abstract The mammalian embryo must undergo dramatic morphogenetic changes to invade the uterine endometrium and achieve implantation. Thus, recapitulation of implantation using in vitro systems is crucial for revealing the mechanisms controlling early development and the main problems compromising human fertility. Experimental systems based on two-dimensional (2D) platforms cannot fully recapitulate the in vivo 3D microenvironments of the embryo. Therefore, here we use collagen grafted onto polydimethylsiloxane (PDMS) based on the uterine mechanics and microstructure to establish a uterus-inspired 3D niche (U3N). Our U3N enables mouse embryos to form egg cylinders at high rate and reach the developmental stages of heartbeat. Moreover, a unique interface forms between the embryo and collagen, showing the invasion of trophoblasts into collagen fires, which simulate the developmental process of implantation. Our findings highlight embryo-substrate interaction as a key characteristic of post-implantation development in vitro and as an important design parameter of 3D conditions for embryo culture.