Cell mapping and mini placentas reveal new details about human pregnancy

Researchers have mapped placental development to understand why pregnancy disorders occur.


Cells are the fundamental building blocks of life, but we still need to understand all of the cells in the human body fully. They must describe all of the functions of cells or comprehend the networks that control their activities with maps of the various cell types, their molecular properties, and their locations within the body.

Researchers from the University of Cambridge, the Wellcome Sanger Institute, the Friedrich Miescher Institute for Biomedical Research (FMI), Switzerland, the European Molecular Biology Laboratory’s European Bioinformatics Institute (EMBL-EBI), and collaborators have created an in-depth picture of how the placenta develops and communicates with the uterus.

The study, published today in the journal Nature, is part of the Human Cell Atlas initiative, which aims to map every cell type in the human body. It informs and enables the development of human placental experimental models.

Anna Arutyunyan, the co-first author at the University of Cambridge and Wellcome Sanger Institute, said, “For the first time, we have been able to draw the full picture of how the placenta develops and describe in detail the cells involved in each of the crucial steps. This new level of insight can help us improve laboratory models to continue investigating pregnancy disorders, which cause illness and death worldwide.”

The placenta is a fetal organ that facilitates vital functions such as fetal nutrition, oxygen and gas exchange, and infection protection. Understanding normal and abnormal placentation at the molecular level can help answer questions about disorders such as miscarriage, stillbirth, and pre-eclampsia. Scientists built on previous research into the early stages of pregnancy to capture the process of human placental development.

Even though pregnancy disorders cause illness and death worldwide, many of the processes in pregnancy are not fully understood. This is partly due to the difficulty of studying the process of placentation in humans. While animal studies are helpful, they have limitations due to physiological differences.

The placenta forms tree-like structures that attach to the uterus during development. The outer layer of cells, known as trophoblast, migrates through the uterine wall, transforming the maternal blood vessels to establish a supply line for oxygen and nutrients.

This study uncovered the entire path of trophoblast development, indicating what could go wrong in disease and describing the involvement of multiple cell populations, including maternal immune and vascular cells.

Professor Ashley Moffett, the co-senior author at the University of Cambridge Department of Pathology, said, “This research is unique as it was possible to use rare historical samples encompassing all the stages of placentation occurring deep inside the uterus. We are glad to have created this open-access cell atlas to ensure that the scientific community can use our research to inform future studies.”

It also compared these findings to laboratory-grown placental trophoblast organoids, known as “mini-placentas.” They discovered that the majority of the cells found in the tissue samples could be seen in these organoid models. Some later trophoblast populations are not visible and are likely to form in the uterus only after receiving signals from maternal cells.

The team focussed on the role of one understudied population of maternal immune cells known as macrophages, which release communication signals that regulate placental growth.

The insights from this research can help develop effective lab models to study placental development and facilitate new ways to diagnose, prevent, and treat pregnancy disorders.

The research was funded by Wellcome, The Royal Society, and the European Research Council.

Journal Reference:

  1. Arutyunyan, A., Roberts, K., etal. Spatial multi omics map of trophoblast development in early pregnancy. Nature. DOI: 10.1038/s41586-023-05869-0


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