'Mini placentas' may reveal roots of pregnancy disorders like preeclampsia

Miniature placentas grown in the lab may be helping reveal crucial steps in how the temporary organ successfully invades the uterus, according to a new study. This research could help improve scientists' understanding of pregnancy disorders, like preeclampsia.

The scientists behind the new research previously showed that their "mini placentas" could fool a pregnancy test by secreting a hormone made by full-size placentas. They developed the tiny organs to study placental development, a crucial part of early pregnancy that can lead to serious complications if it gets derailed.

Studying early placental development in people is difficult — people don't usually know they're pregnant at that stage, and current technologies make it hard to collect data without potentially disrupting the pregnancy. Studying animals' placentas isn't fruitful because they form differently from those of humans.

Now, in their new study, published Jan. 17 in the journal Cell Stem Cell, the researchers identified a group of proteins that appear key to placental development. They also discovered that placenta cells exposed to these proteins switch on genes that are thought to help support the blood flow and implantation of the placenta.

The results suggest that the highlighted proteins could be crucial for a healthy pregnancy and that their dysfunction might contribute to pregnancy disorders, such as preeclampsia.

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The study is "a first example really of how you can do an experiment on a human placenta, which … people have never been able to do before," said Ashley Moffett, a professor of reproductive immunology at the University of Cambridge in the U.K. and senior author of the study.

The mini placentas grown by Moffett and her colleagues specifically mimic trophoblasts, cells of the growing fertilized egg that give rise to a large part of the placenta. The team produced the "trophoblast organoids" by taking cells from human placentas and growing them in a chemical environment similar to what they would be exposed to during pregnancy. The result is a 3D structure that contains a variety of cells found in the placenta.

For this study, the researchers exposed the organoids to a cocktail of four proteins made by "uterine natural killer cells," a type of immune cell unique to the uterus that clusters where the placenta implants. Previous work by the lab suggested the proteins might influence trophoblast development. People who make more of them are less likely to develop preeclampsia, which is marked by high blood pressure, high levels of protein in urine, and sometimes organ damage in a pregnant person.

In response to these proteins, the organoids switched on genes tied to regulating blood flow to the placenta, absorbing nutrients and dampening inflammation. Moffett said many of these genes were also associated with preeclampsia, in that the authors found that their expression is lower in samples from people who developed the condition, compared to those who didn't.

"I think what this is pointing to are the pathways that people now really need to focus on, that are important in the development of these diseases," Moffett said.

The new study has several limitations, including that it examined all four proteins at once, rather than separately, said Myriam Hemberger, a professor in the Department of Biochemistry and Molecular Biology at the University of Calgary in Canada who was not involved with the study. Future research could examine them individually to see if they have different effects, she told Live Science.

In the current work, it's also hard to know if the researchers used the same concentrations of proteins that individual cells within trophoblasts would be exposed to in early pregnancy, Hemberger added.

Follow-up studies could help confirm the link between these proteins and preeclampsia, since the researchers examined relatively few genes they think may be associated. They could also examine whether different proteins like the ones studied might be linked to specific subtypes of preeclampsia — for instance, could they find common proteins in the cell samples of patients who have the same subtype?

The research highlights "how can we now use this data, as well as the organoid models, to actually gain tractable insights into … preeclampsia," Hemberger said.

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