In vitro systems have been used extensively to study early embryonic development. However, it has been impossible to develop ungulate blastocysts after they hatch from the zona pellucida up to symmetry-breaking stages. In ungulates, symmetry breaking occurs in a flat embryonic disc like that of humans. Now, Priscila Ramos-Ibeas, Pablo Bermejo-Álvarez and colleagues identify in vitro conditions for culturing ovine embryos until the early stages of gastrulation. Using a non-adherent surface together with N2B27 media supplemented with Activin A and ROCK inhibitor, the authors can culture embryos for up to 14 days. The cultured embryos display the same developmental features as embryos that develop in vivo, such as the maintenance and polarisation of epiblast cells, trophoblast proliferation, hypoblast migration and the onset of mesoderm specification. On day 14, the in vitro embryos are slightly developmentally delayed compared with their in vivo counterparts. For example, the spherical shape and transcriptome of the cultured day 14 embryos resemble E11 embryos in vivo, whereas features such as epiblast polarisation, mesoderm specification and onset of gastrulation make them comparable with E12.5 embryos. Together, these data make it possible to interrogate ovine pre-implantation development, providing a platform to improve reproductive success in farm animals and a system for modelling human development.
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