Extended embryo culture: illuminating a black box of early development in ruminants

Pregnancy losses due to early embryonic mortality remain a major concern in farm ungulates, including cattle, sheep, pigs and goats. The majority of these losses occur during conceptus elongation, a developmental phase unique to ungulates that follows blastocyst hatching. This stage entails complex cell differentiation, proliferation, and migration processes, leading to the rapid expansion of the extraembryonic membranes (EEMs), namely the trophoblast and the hypoblast, and the formation of the embryonic disc (ED) from the epiblast. Despite its biological and economic relevance, the molecular mechanisms regulating embryo development beyond the blastocyst stage, particularly those governing ED formation, remain poorly understood. Fortunately, recent advances in extended culture systems are enabling the study of these processes entirely in vitro, reducing the need for experimental animals. In this review, we highlight key interspecies differences in early embryogenesis across mammalian species. We discuss the progression and refinement of extended embryo culture systems, from early pioneering efforts to the latest advances, with a specific focus on ruminant species, including cow and sheep. Lastly, we review recent functional studies leveraging extended embryo culture systems in ruminants to elucidate the molecular pathways controlling post-hatching development.