Modeling human embryo implantation in vitro
Matteo A. Molè, Sarah Elderkin, Irene Zorzan, Christopher A. Penfold, Nicole Horsley, Alexandra Pokhilko, Max Polanek, Andrea Palomar, Molika Sinha, Yang Wang, Alicia Quiñonero, Charalampos Androulidakis, Richard Acton, Kathryn Balmanno, Anneliese Jarman, Jhanavi Srinivasan, Adam Bendall, Sara Morales-Alvarez, Roberto Yagüe-Serrano, Katie Heywood, Stephen Harbottle, Mina Vasilic, Suzanne Cawood, Srividya Seshadri, Paul Serhal, Lauren Weavers, Ippokratis Sarris, Anastasia Mania, Rachel Gibbons, Lucy Laurier, Immaculada Sánchez-Ribas, Amparo Mercader, Pilar Alamá, Anthony Hoa Bui, Graham J. Burton, Tereza Cindrova-Davies, Ridma C. Fernando, Afshan McCarthy, Lusine Aghajanova, Liesl Nel-Themaat, Ruth B. Lathi, Simon J. Cook, Kathy K. Niakan, Alexander R. Dunn, Francisco Domı́nguez, Peter J. Rugg‐Gunn
Abstract
Implantation of a human embryo into the endometrium is a crucial event in gestation, as it marks the initiation of a pregnancy and is prone to high failure rates. We have limited understanding of these stages because of the inaccessibility of implanting embryos and the lack of suitable model systems. Here, we establish an in vitro model that recapitulates the luminal, glandular, and stromal compartments of the superficial layer of receptive human endometrium. Human embryos and blastoids implant into the endometrial model, achieving post-implantation hallmarks including advanced trophoblast structures that underlie early events in placental development. Single-cell RNA sequencing of the embryo-endometrial interface at day 14 uncovers predicted molecular interactions between conceptus and endometrium. Disrupting signaling interactions between extravillous trophoblast and endometrial stromal cells caused defects in trophoblast outgrowth, demonstrating the importance of crosstalk processes to sustain embryogenesis. This platform opens the opportunity to investigate early stages of human embryo implantation.