Developmental biology: Platform models early human pregnancy

A microengineered system which can model the multicellular events that occur during early pregnancy, is presented in a paper published in Nature Communications. The system reconstructs the maternal-fetal interface and could aid our understanding of the mechanisms underlying successful embryo implantation.

The successful establishment of pregnancy requires the embryo to connect and implant into the maternal endometrium layer of the uterus, which supports the pregnancy. Previous research has indicated that abnormalities in this process may lead to complications, such as preeclampsia. However, this has been difficult to assess in humans due to ethical concerns, and animal or cell models fail to mimic some cellular complexities.

Dan Dongeun Huh, Monica Mainigi and colleagues designed an implantation-on-a-chip system to reconstruct the maternal-fetal interface. The system uses a microfluidic platform consisting of a fetal chamber and a maternal vascular chamber connected by an extracellular matrix channel, combined with extravillous trophoblast cells (EVTs — a subset of placental cells involved in the attachment of the placenta to the uterus) isolated from donated clinical specimens. Using this platform, the authors were able to observe the migration of EVTs and track the movement towards the blood vessels in the maternal compartment. The authors were also able to investigate the effect of different environmental parameters and the presence of maternal stromal cells (connective tissue) and immune cells on EVT migration. Finally, they analyze proteins expressed and secreted by the maternal uterine cells and how the maternal tissue remodels to accommodate incoming fetal cells.

The authors suggest their findings present an advance in our ability to model early human pregnancy and may enable the development of platforms to explore human reproduction.