CRCHUM researcher Sophie Petropoulos and her team reveal for the first time that the guinea pig pre-implantation embryo is very similar to the human embryo, spurring a better understanding of infertility and early human development.

The first few days of a human embryo’s development, known as pre-implantation, are important. It’s when the first cells are formed, and these decide if the embryo can survive, how it will implant in the womb and how the tissues of the fetus will develop.

Today there are still logistical, ethical and legal limitations to using human embryos for research purposes, so scientists use alternative models including stem cell-based and animal models.

In a new study published in Nature Cell Biology, Sophie Petropoulos, a researcher at both Université de Montréal’s affiliated hospital research centre, the CRCHUM, and the Karolinska Institutet, in Sweden, shows that guinea pigs can serve as a reliable and robust small animal model to enhance our understanding of two key areas of research: comparative biology and human embryogenesis.

The guinea pig has long been used for studies in developmental biology and is very similar to humans in terms of general physiology. It is also the only small animal that, in females, goes through a full estrous cycle as women do, undergoes a similar implantation process and develops similar placentas.

“Despite these noted similarities, preimplantation development had not been studied,” said Petropoulos, an associate professor at UdeM and holder of a Canada Research Chair in Functional Genomics of Reproduction and Development. “Our lab is focused on understanding infertility and early human development, so we wanted to identify a model that we could use to answer our questions.”

A complete atlas of genes

“In our study, we used a technique known as single-cell RNA sequencing to produce a complete atlas of the genes involved in the guinea pig pre-implantation development, and examined their timing and expression. We also inhibited and activated signalling pathways to see how these genes could affect embryo development” she said. “When we compared the development of the guinea pig embryo to our previous work, we were very surprised by its striking resemblance to early human embryogenesis.”

That discovery opens new possibilities for understanding women’s infertility and for developing therapeutics to help ensure a healthy pregnancy, said Petropoulos, who was aided in her study by its two first authors: Jesica Romina Canizo, a research associate in Petropoulos’ lab at the CRCHUM, and Cheng Zhao, a research specialist in her lab at the Karolinska Institutet.

“The guinea pig model can help scientists understand how early exposure to drugs or environmental disruptions affect the health outcomes for babies in the long term, or why some women have recurring implantation failure,” Petropoulos said.

She and her team have now started to study post-implantation embryo development and gastrulation, during which all the organs and tissues of the human body are formed. With 80 per cent of pregnancy failures occurring in the first trimester, scientists are keen to understand this period of human development, known as the “black box”.

In the long term, the guinea pig preimplantation embryo model might provide extremely useful information about the best conditions for the development of healthy embryos and fetuses, Petropoulos and her team believe. This could help to improve fertility treatments and assist reproductive technologies.

Science writing: Bruno Geoffroy