The guinea pig serves as an alternative model to study human preimplantation development.

Preimplantation development is an important window of human embryogenesis. However, ethical constraints and the limitations involved in studying human embryos often necessitate the use of alternative model systems. Here we identify the guinea pig as a promising small animal model to study human preimplantation development. Using single-cell RNA-sequencing, we generated an atlas of guinea pig preimplantation development, revealing its close resemblance to early human embryogenesis in terms of the timing of compaction, early-, mid- and late-blastocyst formation, and implantation, and the spatio-temporal expression of key lineage markers. We also show conserved roles of Hippo, MEK-ERK and JAK-STAT signalling. Furthermore, multi-species analysis highlights the spatio-temporal expression of conserved and divergent genes during preimplantation development and pluripotency. The guinea pig serves as a valuable animal model for advancing preimplantation development and stem cell research, and can be leveraged to better understand the longer-term impact of early exposures on offspring outcomes.