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Communication between the maternal endometrium and developing embryo/conceptus is critical to support successful pregnancy to term. Studying the peri-implantation period of pregnancy is critical as this is when most pregnancy loss occurs in cattle. Our current understanding of these interactions is limited, due to the lack of appropriate in vitro models to assess these interactions. The endometrium is a complex and heterogeneous tissue that is regulated in a transcriptional and translational manner throughout the oestrous cycle. While there are in vitro models to study endometrial function, they are static and 2D in nature or explant models and are limited in how well they recapitulate the in vivo endometrium. Recent developments in organoid systems, microfluidic approaches, extracellular matrix biology, and in silico approaches provide a new opportunity to develop in vitro systems that better model the in vivo scenario. This will allow us to investigate in a more high-throughput manner the fundamental molecular interactions that are required for successful pregnancy in cattle. The majority of pregnancy loss in cattle (and other mammals) occurs in the peri-implantation period. The contribution of endometrial dysfunction to this loss remains elusive. Furthering our understanding the function/dysfunction of the endometrium is difficult given the lack of in vitro models that appropriately recapitulate the in vivo scenario or allow high-throughput testing of conceptus–maternal interactions. Here we review the current state of the art of in vitro and in silico model development, which will allow us to test the molecular interactions required for pregnancy success in cattle and other mammalian species. Created with BioRender.com. [ABSTRACT FROM AUTHOR]

Implantation in cattle is a key developmental checkpoint for pregnancy success. It involves careful spatiotemporal changes to the transcriptional landscape of the endometrium, with the heterogeneous nature of the endometrium increasing the complexity of understanding of the mechanism involved. Implantation is impacted by the developmental competency of the embryo, use of assisted reproductive technologies, and the environment in which this process occurs. We identify the factors that most impact the implantation process in cattle and highlight how it differs with that in other placental mammals. We propose the major areas that lack evidence are the mechanism(s) by which implantation itself occurs and how different stressors alter this process. Our understanding is hindered by a lack of appropriate in vitro models; however, development of novel 3D tools and available data sets will further elucidate the implantation process. Perhaps more importantly, this will develop methods to mitigate against these stressors to improve implantation success and offspring health.