The earliest stage of human embryo development—known as pre-implantation—is a critical window. During this phase, the first cells form, setting the stage for the embryo’s viability, implantation in the uterus, and the eventual development of fetal tissues.
However, the study of human embryos remains constrained by ethical, legal, and logistical challenges. As a result, scientists often turn to alternative models, including stem-cell-based systems and animal models.
A recent study published in Nature Cell Biology by Sophie Petropoulos, a researcher at both the CRCHUM at Université de Montréal and the Karolinska Institutet in Sweden, reveals that guinea pigs may serve as a reliable and powerful small-animal model for studying two key areas: comparative biology and early human embryogenesis.
Guinea pigs have long been used in developmental biology and share several important physiological traits with humans. Notably, they’re the only small animal to experience a full estrous cycle similar to that of women. They also undergo a comparable implantation process and develop similar placental structures.
“Despite these similarities, pre-implantation development in guinea pigs hadn't been thoroughly explored,” says Petropoulos. “Our lab focuses on infertility and early human development, so we were looking for a model that could help us address some pressing questions.”
Petropoulos, who also holds a Canada Research Chair in Functional Genomics of Reproduction and Development, led the study that may fill that gap.
A Comprehensive Gene Atlas
Using single-cell RNA sequencing, Petropoulos and her team generated a detailed atlas of gene expression during guinea pig pre-implantation development. They tracked when and where specific genes were active and manipulated key signaling pathways to understand how these genes influence early development.
“When we compared guinea pig embryos to our previous work on human embryos, we were surprised by how closely the two aligned,” she notes.
This similarity could have wide-ranging implications for understanding infertility and improving pregnancy outcomes. The study was supported by two key researchers in Petropoulos’ lab: Jesica Romina Canizo at the CRCHUM and Cheng Zhao at the Karolinska Institutet.
According to Petropoulos, the guinea pig model could help scientists explore how early exposure to drugs or environmental stressors influences long-term health outcomes. It may also shed light on why some women experience recurrent implantation failure.
Her team is now expanding its research into post-implantation development and gastrulation—the stage when all tissues and organs begin to form. This period remains one of the least understood in human development, often referred to as a “black box,” despite the fact that 80% of pregnancy losses occur during the first trimester.
In the long term, insights from the guinea pig model could help define the conditions needed for healthy embryo and fetal development. That knowledge could be instrumental in advancing fertility treatments and improving reproductive technologies.
Source:
Journal reference:
Canizo, J. R., et al. (2025) The guinea pig serves as an alternative model to study human preimplantation development. Nature Cell Biology. doi.org/10.1038/s41556-025-01642-9.