Emerging in vitro platforms and omics technologies for studying the endometrium and early embryo-maternal interface...

Human reproductive success relies on the intricate interplay between the developing embryo and the maternal endometrium. These highly-coordinated interactions facilitate implantation, setting in motion a series of developmental programs to establish a sustained fetal-maternal interface. Understanding endometrial function and the early human embryo-maternal dialogue is thus an important prerequisite for refining clinical approaches to alleviate implantation failure, early pregnancy loss and other obstetric complications. Yet, many mediators of implantation remain elusive. Driven by endocrine factors, interactions at the embryo-maternal interface are tightly regulated and highly complex. Coupled to the inaccessibility of the in vivo environment and scarcity of research material, studying human implantation remains exceptionally challenging. Nevertheless, the field continues to gain momentum. Cutting-edge omics technologies and high-resolution imaging have revealed important structural and functional insights into endometrial biology, while emerging bioengineering tools are enhancing our ability to model the synergies and individual features of the embryo-maternal environment. Novel in vitro platforms using human cells and embryos are considerably more accessible and easier to manipulate compared to in vivo approaches, enhancing our ability to capture specific stages of implantation. This review aims to showcase current and emerging technologies used to study human endometrial biology and the early embryo-maternal interface, including single cell omics approaches, bioengineered endometrial models and embryo-endometrium co-culture platforms. We highlight the value of these approaches and provide our perspective on the current challenges faced by the field. Recognizing the physiological scope of these emerging technologies will be key for utilizing their full potential and driving future innovation.