Shedding light into the black box: Advances in in vitro systems for studying implantation

Implantation represents a critical step for embryonic development and pregnancy. Its success depends on the complex interplay between a receptive endometrium and a competent embryo. Implantation-related events remain hardly accessible, making implantation a true "black box" in developmental biology. Improved in vitro models are becoming useful experimental tools, as they are considerably more accessible than in vivo models, easier to manipulate, and permit the use of human cells or tissues, thus increasing the translational value of the studies. In this Review, we briefly summarize the relevant cell types and structures involved into the process of implantation, in order to outline which compartments are indispensable for creating the perfect in vitro model. We also critically address advantages and limitations of available models and assess their application potential. Moreover, we examine the chances and challenges brought by the latest approaches to recapitulate the endometrial compartment, as well as by peri-implantational embryoids.